1.0 Preface

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1.1 PURPOSE OF GUIDELINES
These guidelines were compiled by a multidisciplinary group at the request of the chairman of the British Society of Gastroenterology's Clinical Services Committee. The prime targets for these guidelines are consultant gastroenterologists, specialist registrars in training, and general practitioners. The purpose is to identify and inform the key decisions to be made in the management of patients thought to have functional diseases of the gut. As these comprise the commonest conditions seen by gastroenterologists, the working party represented a wide spectrum of practitioners in gastroenterology, including gastroenterologists from both district general hospitals and tertiary referral centres, as well as primary care practitioners, psychiatrists, psychologists, and dietitians.

1.2 SPECIFIC DIFFICULTIES
Compared with producing guidelines for the management of well defined diseases such as peptic ulcer where there is a clear disease entity, an obvious end point, and highly effective treatments, drawing up guidelines for functional gastroenterological disorders has had many difficulties. Clinical trials have been difficult to design as the conditions being treated are highly variable with many possible end points, and most therapies only marginally more effective than placebo. Early trials were difficult to evaluate because of inadequate patient definition so that many questions have yet to be addressed with good quality randomised controlled clinical trials. Most of our recommendations are therefore supported by clinical experience rather than randomised controlled clinical trials. Finally, because functional diseases, although potentially debilitating, are non-fatal there are few uniformly available audit measures such as mortality or survival times by which to judge or compare different treatment regimens in different areas of clinical practice.

1.3 PROCESS OF GUIDELINE CREATION
The co-chairmen were approached by the chairman of the British Society of Gastroenterology's Clinical Services Committee and invited to form a working party. Members were chosen to be broadly representative of clinicians and academics with a long term interest and publication record in the field of functional bowel disease. A preliminary document was produced and subsequently modified during several meetings of the working party. The initial document was further developed after a comprehensive literature search by Dr J Jones, specialist registrar in the Department of Gastroenterology, University Hospital Nottingham. This involved a review of personal and electronic databases including Medline, PubMed and Ovid using keywords such as "functional disease", "dyspepsia", "irritable bowel syndrome", "spastic colon", and "irritable colon". Further information was obtained from references in quoted papers and by contacting relevant pharmaceutical companies, and a total of 2521 relevant papers were identified. This preliminary document was modified after several reviews by members of the working party and submitted to the Clinical Services Committee for independent review. Members of the British Society of Gastroenterology Council then further reviewed the document. Comments from these reviewers and representatives of the IBS patient group, the IBS network, have been incorporated into the final version

1.4 CATEGORIES OF EVIDENCE
The strength of evidence used in the formulation of these guidelines was graded according to the following system, which has been used in previous British Society of Gastroenterology (BSG) guidelines. However, in the context of functional diseases it should be recognised that this tends to over value the contribution of randomised, double blind, placebo controlled trials at the expense of studies of psychological treatments, which are difficult or impossible to double blind.

Grade	Ia: evidence obtained from meta-analysis of randomised, double blind, placebo controlled trials.
Grade	Ib: evidence obtained from at least one randomised, double blind, placebo controlled trial.
Grade	IIa: evidence obtained from at least one well designed placebo controlled study without randomisation.
Grade	IIb: evidence obtained from at least one other type of well designed quasi-experimental study.
Grade	III: evidence obtained from well designed non-experimental descriptive studies such as comparative studies, correlation studies, and case studies.
Grade	IV: evidence obtained from expert committee reports or opinions, clinical experiences, or respected authorities.

1.5 GRADING OF RECOMMENDATIONS
The strength of each recommendation depends on the category of the evidence supporting it, and is graded according to the following system:

Grade	A: requires at least one randomised controlled trial as part of the body of literature of overall good quality and consistency (evidence categories Ia, Ib).
Grade	B: requires the availability of clinical studies without randomisation (evidence categories IIa, IIb, III).
Grade	C: requires evidence from expert committee reports or opinions, or clinical experience of respected authorities, in the absence of directly applicable clinical studies of good quality (evidence category IV).

1.6 SCHEDULED REVIEW OF GUIDELINES
It is proposed that these guidelines be presented on the BSG world wide web page and be available for comment. They should be reviewed at 2-3 year intervals taking into account feedback from both public and profession, as well as new scientific evidence. Comments on these guidelines should be sent to Dr R C Spiller or Dr A Forbes.

1.7 SUMMARY OF AUDIT GOALS
Audit of the management of non-fatal conditions requires assessment of somewhat subjective quality of life parameters rather than the familiar morbidity and mortality statistics. Ideally patients with functional gastrointestinal disease would have a diagnosis established with the minimum of investigations without missing significant alternative diagnoses. They would then enter a treatment programme with high efficacy which reduced the need for further consultations and procedures. Specific audit goals might include:

• Achieving an acceptably low proportion of missed non-functional diagnoses during one year of follow up, which would be lower for serious diagnoses such as cancer (<1%) while for less serious diagnoses such as lactose intolerance <10% might be acceptable.
• Ensuring a minimum number of patients aged <45 years undergo negative barium studies during diagnostic work up.
• Reducing the number of work days missed through ill health after functional diagnosis made compared with before diagnosis.
• Reducing the frequency of physician visits for both gastrointestinal (GI) and non-GI related complaints after diagnosis and treatment.
• Improving quality of life after consultation, investigation, and management.

	2.0 Summary

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2.1 OVERVIEW
Functional gastrointestinal disorders (FGD) are the result of disordered GI function in the absence of known pathology of structure. FGD are among the commonest medical conditions; functional dyspepsia (FD) and irritable bowel syndrome (IBS) account for 40-60% of referrals to gastroenterology outpatient clinics.

2.2 FOCUS OF THIS REPORT
The specific recommendations which follow refer to IBS but because of extensive overlap, much of the general recommendations also apply to other functional disorders including non-ulcer dyspepsia and non-cardiac chest pain. However, to avoid lack of focus in this report, specific recommendations for these latter conditions will be addressed in separate guidelines.

2.3 DIFFERENCES BETWEEN PRIMARY AND SECONDARY CARE
Most published studies of IBS are from academic units describing referred patients who differ significantly from those seen in general practice, being less likely to accept a psychological explanation of their symptoms and more convinced they have organic disease.

2.4 EPIDEMIOLOGY
IBS is common, affecting 9-12% of the population with a female/male ratio ranging from 1.1 to 2.6 depending on the weight given to individual symptoms. Age and race have no consistent effect on incidence of symptoms.

2.5 AETIOLOGY
Psychological morbidity Most cases seen in general practice do not have major psychological morbidity. However, those who progress to outpatients have a higher incidence of psychological symptoms and psychiatric disease.

2.6 CLINICAL FEATURES
Gastroenterological These include recurrent abdominal pain associated with disturbed bowel habit. Various symptomatic criteria have been defined (see table 1) for clinical trial purposes but do not match the symptoms of all patients. Other criteria such as disturbed defecation are supportive but not essential.

2.7 DIAGNOSIS
Working diagnosis This can usually be safely made in general practice on the basis of typical symptoms, a normal physical examination, and absence of sinister features (weight loss, rectal bleeding, nocturnal symptoms, or anaemia). This diagnosis should be confirmed in general practice by observation over time.

2.8 WHEN TO REFER
If symptoms are atypical, the history short, or the patient over 45, it is usually appropriate to perform further investigations, often via hospital referral.

2.9 INVESTIGATION AFTER REFERRAL
Sigmoidoscopy Those referred to hospital will usually require a sigmoidoscopy if there are colonic symptoms. Any abnormality noted should be biopsied, as should all patients with diarrhoea to detect unsuspected microscopic colitis.

2.10 PROGNOSIS
Once a functional diagnosis is established the incidence of new non-functional diagnoses is extremely low.

2.11 MANAGEMENT AND TREATMENT

2.11.1 Explanation
Positive diagnosis and reassurance Most patients will be managed in general practice. The mainstay of management should be a positive diagnosis with an explanation of symptoms and their possible causes, in language the patient can understand with reassurance of a benign prognosis.

2.11.2 Dietary manipulation
Diet advice Self-imposed dietary restrictions to avoid pain or diarrhoea are common but may be inappropriate. True allergy is rare but intolerance of poorly absorbed carbohydrate, especially lactose and fructose, is well recognised. Excessive caffeine containing beverages may be responsible for some symptoms.

2.11.3 Psychological therapies
Identify psychological disorders This involves a careful history of psychological features, including disorders of mood and sleep and any association of thoughts or feelings with symptoms.

2.11.4 Pharmacological treatments
Drug treatments These have a substantial short term response rate, most of which is due to a non-specific placebo component. Specific benefit is seen in only a small proportion of patients.

2.12 FUTURE RESEARCH NEEDS
Compared with other fields, the evidence base is weak and much of the evidence quoted here is at the level of clinical consensus only. Much more research is needed into these common conditions before we can give confident answers to many important clinical questions.

	3.0 Spectrum of functional gastroenterological disorders

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Functional gastroenterological disorders (FGD) are defined by symptoms in the absence of known structural pathology. They have no specific disease marker and their symptoms overlap with those of other diseases. Experienced clinicians often diagnose these disorders on symptoms alone but as functional disorders are so much more common than organic diseases, any diagnostic strategy is likely to have a deceptively high positive predictive value. Typical symptoms include abdominal pain or discomfort and, particularly in hospital patients, a range of non-specific symptoms such as lethargy, anxiety, disturbed sexual function, and disordered sleep. The majority of patients have some features of psychological morbidity, particularly mood disorder.

As there are no specific disease markers, FGD have been categorised according to the likely site of the principal disorder. This ranges from the oesophagus in functional dysphagia, the upper gastrointestinal tract in FD, the colon in IBS, to the anorectum in proctalgia fugax and obstructed defecation. Attempts have been made to further subdivide these disorders into ulcer-like, dysmotility-like, or reflux-like in functional dyspepsia (FD) and into diarrhoea predominant or constipation predominant in the case of IBS. These distinctions reflect the poor understanding of functional disorders rather than evidence of different pathological processes. In reality there is frequent symptom overlap and poor site specific correlation with functional investigations, such as manometry, balloon distension threshold,^1 2 intestinal transit, and gastric emptying studies. The same patients may report symptoms typical of both IBS and the various types of FD with variable prominence of the different symptoms over time.³ It follows therefore that the overall approach to these conditions should be similar.

3.1 SOCIAL IMPACT
Despite the benign nature of these disorders, many functional symptoms such as vomiting, choking, bloating, faecal urgency, incontinence, diarrhoea, flatulence, and borborygmi can restrict social activities and substantially reduce quality of life. Chronic food related pain may lead to refusal of social invitations, while fears about the need for frequent defecation may substantially restrict travel and work. Over 40% of patients report avoidance of some activities including work, travelling, socialising, sexual intercourse, domestic and leisure pursuits, and eating certain foods as a consequence of their symptoms.⁴ Average work days lost in the USA per year by patients with FGDs were 14.8 compared with 8.7 in the asymptomatic population.⁵ It is this reduction in their quality of life, rather than individual symptoms, which most determines how patients rate the severity of their functional bowel diseases.⁶

There is often a complex relationship between symptoms (table 1) and restricted social activities, with some patients in effect hiding (usually subconsciously) behind these symptoms to avoid situations they find difficult. Patients may experience anxiety and disturbed sleep, with associated lethargy and an "inability to get on with their lives", such that in the worse cases the condition comes to dominate their existence. Difficulty in confirming the diagnosis may lead to further worry and doubt, with numerous visits to doctors and repeated unpleasant tests. A further burden, especially in women, is the risk of unnecessary surgery such as cholecystectomy or hysterectomy, which may aggravate the existing disorder, as well as adding their own specific postoperative complications such as scar pain, adhesions, and surgery related changes in bowel habit.

3.2 FOCUS ON THE IBS AS A MODEL FOR FGD
These guidelines concentrate on IBS as this symptom complex is the commonest and best studied of the FGD. However, the principles of investigation and management, particularly of its psychological features, are applicable to all functional disorders. Epidemiology and possible aetiology are discussed in some detail as the most important part of management is explanation, reassurance, and dealing with the associated psychological problems.

	4.0 Epidemiology

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4.1 SEX AND AGE
IBS symptoms are about twice as common in women as men (tables 2-4). The variability in the sex ratio (1.1-2.6) may depend on the weight given to various symptoms as all studies agree that straining and passage of hard stools are commoner in women while frequent and loose stools are commoner in men.¹¹ Although the frequency of those reporting abdominal pain together with two or more Manning criteria declined with age over 45 in most studies,^5 12-14 the influence of age appears small and was not seen in a recent large UK study which included over 1800 subjects.¹⁵ Hence advancing age should certainly be no bar to the diagnosis of IBS although the increasing incidence of other diseases with similar symptoms argues for greater caution in making the diagnosis in the elderly.

4.2 SEVERITY
As the number or frequency of symptoms required for making the diagnosis increases, the calculated prevalence falls (table 2, 3). Most studies have used either the Rome I criteria or three Manning criteria (which produce closely comparable diagnostic rates). This results in a prevalence of 1.5-12.1% for men and 5.2-19.1% for women (table 4).

4.3 ETHNIC DIFFERENCES
Ethnic differences have been found in a few studies that have made direct comparisons. IBS appears to be more common in Japan than Holland (25% v 9%)¹⁶ and in Whites compared with Hispanics in the USA (21.8% v 16.9%)¹⁷ but similar in US Whites and Blacks.⁸ One study of students in Nigeria showed a particular high prevalence of symptoms (48% in women and 24% in men using two Manning criteria) but this may have been due to the high incidence of gastrointestinal infections in this population.¹⁸ By contrast, subjects from rural Thailand appear to have a much lower risk.¹⁹ Cultural factors including diet and socioeconomic status are important; thus in the bicultural city El Paso on the US/Mexican border, US Whites are more likely to report symptoms than Hispanics, but after controlling for socioeconomic and dietary differences this ethnic difference was no longer significant.²⁰

	5.0 Aetiology

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5.1 OVERVIEW
It is highly likely that within the group of patients with functional bowel disease there are as yet unrecognised infectious and other organic causes of bowel disturbance. We should not therefore expect all patients to show similar features or predisposing factors. However, for many patients the two most consistent, and probably interrelated, characteristics are psychological morbidity and visceral hypersensitivity. A substantial minority may relate the onset of symptoms to an acute gastrointestinal illness, while a further minority report that specific dietary components precipitate symptoms.

5.2 PSYCHOLOGICAL MORBIDITY
Most cases seen in general practice do not have major psychological morbidity. Those who progress to outpatients have a higher incidence of psychological symptoms and psychiatric disease, the most floridly abnormal being found in long term follow up in those attending academic departments.²⁴ Compared with healthy controls, these IBS patients have higher scores for anxiety, hostile feelings, sadness, depression, interpersonal sensitivity as well as more sleep disturbance.^25-28 However, part of this is due to the fact that more anxious patients are more likely to seek a second opinion as IBS sufferers who do not consult any doctor are not psychologically different from controls.²⁹ Compared with outpatients with organic gastroenterological disease, there are no consistent differences and psychiatric features cannot be used reliably to distinguish functional from organic disease.^30 31

Several studies have investigated the prevalence of adverse life events and in particular sexual abuse in these patients. More than 50% linked the onset of their symptoms to a stressful event such as employment difficulties, family death, a surgical procedure, or marital stress, and a similar proportion reported concurrent social problems relating to work, finances, housing, and personal relationships.⁴ A history of sexual abuse, often combined with physical abuse, both in childhood and subsequent adult life has been reported in 20-30% of patients with IBS, significantly more commonly than in the general population (<10%) or in patients with organic disease (14%).^32 33 Adverse life events prior to the onset of IBS are as common as in patients with deliberate self-poisoning and significantly more common than in patients with organic gastrointestinal disease.³⁴ Significantly, the psychiatric illness or adverse life event preceded the onset of the bowel disorder in two thirds of patients.²⁸

5.3 ABNORMAL ILLNESS BEHAVIOUR
Not all patients with symptoms consistent with IBS consult a doctor; consultation rates vary from 10% to 50% depending on age and sex.^13 15 35 As expected, patients with more symptoms and more severe pain were more likely to consult,¹⁵ as were those with more psychological symptoms.^36 37 This relationship between psychosocial disorders and frequent attendance at outpatient clinics is true for many disorders and is not unique to IBS.³⁰ As expected, those who reach outpatients are more likely to believe that their illness is not stress related and are therefore more fearful of organic disease.³⁸

Patients with FGD also consult their doctors more often for non-GI complaints than patients without FGD.⁵ Non-gastroenterological features such as lethargy, poor sleep, fibromyalgia, backache, urinary frequency, and dyspareunia are more frequent in IBS and supportive of the diagnosis. Patients with IBS and lower abdominal pain are over represented in gynaecology and surgical outpatients³⁹ but are less likely to have recognisable pathology⁴⁰ and more likely to undergo surgery.^41 42 Studies of this abnormal illness behaviour have found a record of multiple somatic complaints and inappropriate consultations for minor illnesses.⁴³ There were significantly higher abnormal illness behaviour scores in IBS patients compared with those with organic disease or patients consulting specifically for depression.²⁷ This negative interpretation of innocent sensations is consistent with the observation that patients with IBS were biased towards remembering terms with negative connotations.⁴⁴ This may well explain why objective measures of disturbed function such as rapid colonic transit or increased rectal sensitivity relate so poorly to symptoms but relate better to psychological features.⁴⁵

Patients' complaints of ill health may reflect their experience of others with similar symptoms or previous experience of the secondary gain associated with being ill themselves. Studies of children with chronic abdominal pain have found an association with poor health and emotional disorders in their parents.^46 47 People who recalled being given gifts or special foods when they were unwell as a child were more likely to exhibit chronic illness behaviour and more likely to have IBS as adults.⁴³

5.4 EFFECT OF MOOD ON GI FUNCTION
Most people have, at some time or other, experienced the effect of anxiety on gut function, including cramps and diarrhoea. Animal studies have shown that stress inhibits small bowel transit while accelerating colonic transit and causing increased stool frequency.⁴⁸ Depressed patients have delayed small bowel and whole gut transit, with a correlation between transit time and severity of depression, while anxiety is associated with accelerated small bowel transit.⁴⁹ Acute stress is difficult to model in an ethical experiment but in healthy volunteers acute stress disrupts normal fasting motor patterns⁵⁰ and accelerates small bowel transit.⁵¹ It also stimulates the colon of both normal subjects and IBS patients, although until recently it has been difficult to demonstrate any consistent difference between the two groups.^52-54 Over the past decade evidence has accumulated showing that the cathartic effect of severe stress in rats is mediated largely through release of corticotrophin releasing factor.^55-57 This has made it possible to mimic the effect of severe stress on the human colon by using an infusion of corticotrophin releasing factor which increases descending colon motility indices and induces abdominal pain. When this was done, the IBS patients' colonic responses were greater and they experienced more pain than normal subjects,⁵⁸ an interesting finding which needs confirming.

Stress has not been convincingly shown to alter perceptual thresholds to balloon distension⁵⁹ but relaxation and hypnosis can raise the threshold for discomfort, while hyperventilation has been shown to lower discomfort thresholds.⁶⁰

5.5 ABNORMAL AUTONOMIC REACTIVITY IN IBS
Altered autonomic reactivity has been noted in IBS, with decreased vagal tone associated with constipation^61 62 and increased sympathetic activity associated with diarrhoea.⁶³ These observations provide a mechanism whereby psychological abnormalities could be translated into differences in transit. The potential role of autonomic dysfunction in IBS is made more plausible by the report from the Mayo Clinic of eight patients with acute autonomic neuropathies who presented with apparently typical IBS symptoms.⁶⁴

5.6 EVIDENCE OF ABNORMAL GUT MOTILITY IN IBS
Early studies suggested abnormal electrical control activity in the colon⁶⁵ but this was not substantiated by later workers.^66 67 As with non-IBS constipated patients, constipation predominant IBS patients have been reported to have decreased high amplitude propagated colonic contractions.⁶⁸ However, sigmoid contractility is increased in some patients⁶⁹ and this may cause increased resistance to caudal flow. Exaggerated response to emotion has also been reported⁷⁰ but this difference from controls was not consistent,⁷¹ perhaps due in part to the difficulty in inducing strong emotions reliably while remaining within boundaries set by ethical constraints (see preceding section). Inadequate means of scoring and assessing colonic pressure profiles may also contribute to the difficulty in showing consistent differences as transit studies have generally shown fast and slow transit in diarrhoea and constipation predominant IBS, respectively.⁷² However, it should be noted that in spite of fast transit, most stool weights in IBS patients lie within the normal range^73 74 even in those with diarrhoea as their main complaint.^75 76

Interest in possible small bowel abnormalities were stimulated by initial reports that discrete clustered contractions were commoner in IBS and associated with symptoms.^77 78 However, these have not been confirmed by others⁷⁹ although the later study examined only fasting activity when symptoms are less frequent.

Recently there has been an increasing emphasis on altered sensation as the basis for symptoms as it has become clearer that symptoms correlate poorly with objective measures such as stool weight and transit.

5.7 VISCERAL HYPERSENSITIVITY
Patients with FGD exhibit decreased pain thresholds to balloon distension of the gut. This was first described in the rectum of patients with IBS 25 years ago⁸⁰ and subsequently confirmed by others⁸¹ and is often noted with air insufflation during colonoscopy.⁸² Similarly, patients with FD have a lower threshold to balloon distension of the stomach.⁸³ This visceral hypersensitivity is not site specific and has been demonstrated in the oesophagus of patients with IBS as well as in the rectum of patients with FD.⁸⁴ These changes are specific to gut stimulation as somatic pain thresholds to extreme cold or transcutaneous electrical stimulation are either normal or even increased in some studies.^81 84 85 This was thought to indicate an abnormality of mucosal sensitivity in the gut but as studies have become more sophisticated to try to eliminate external influences on patient perception, this opinion has changed. IBS patients are much more likely to show an increased sensitivity when the rectum is distended in a predictable sequence of increasing volumes than when it is distended with volumes chosen in a random iterative method. This indicates a response bias, which may be related to a patient's apprehension of pain rather than any peripheral and objective increase in sensitivity.⁸⁶ These studies suggest that IBS patients describe gut stimuli as unpleasant or painful at lower intensity levels compared with normals, a phenomenon which is likely to originate centrally rather than peripherally.

The central processing of visceral afferents has been assessed using positron emission tomography (PET scanning) and more recently functional magnetic resonance imaging to measure the resulting regional cerebral blood flow. Most of the relevant studies have as yet only been presented in abstract form. The one published study compared the effects of actual and sham distension of the rectum in healthy volunteers and IBS patients on cerebral blood flow. Perception of pain during both actual and simulated delivery of painful stimuli in healthy subjects was associated with activation of the anterior cingulate cortex (ACC) whereas no ACC response was seen with non-painful stimuli. IBS patients in this study showed no consistent activation during either painful or non-painful distension but demonstrated significant activation of a different region, the left prefrontal cortex, when anticipating painful stimulation due to sham distension.⁸⁷ This and other evidence suggests that normally the ACC has an important role in mediating the affective qualities of visceral pain, both intestinal and cardiac, and that this response is abnormal in IBS and other painful functional disorders such as fibromyalgia. Subsequent studies have produced conflicting data so plainly this area is still evolving. Abnormal central processing may provide a mechanism which could explain the association between IBS and mood, psychological stressors as well as disease beliefs and expectations.

5.8 POSTINFECTIVE BOWEL DYSFUNCTION
A subgroup of IBS patients report that their symptoms began after an acute gastrointestinal illness, a group which appeared to have a slightly better prognosis in two retrospective analyses.^88 89 Persistent bowel dysfunction was noted in 25% of patients following documented Campylobacter, Shigella, and Salmonella^90 91 gastroenteritis. Two separate studies reported that 38% and 29% of patients with enteritis developed IBS.^45 91 Factors predisposing to persisting symptoms included a physically more severe acute illness⁹⁰ as well as greater anxiety and adverse life event scores in the six months leading up to the acute illness.⁴⁵ Increased sensitivity to rectal distension was also reported after the infectious illness.⁴⁵ While macroscopically normal, microscopic abnormalities are detectable in rectal biopsies using special stains, the significance of which is under investigation. This phenomenon is not unique to IBS, cystitis being another example of a disease in which inflammation appears to increase visceral sensitivity.⁹² The conclusions of these studies have recently been supported by a prospective study of over 584 000 patients in whom it was shown that when a range of demographic details were examined, a bout of culture positive bacterial gastroenteritis emerged as the strongest predictor of new onset IBS, with a relative risk of 11.9 (95% CI 6.7-21).⁹³

5.9 DIET
Patients often relate their functional symptoms to certain foods and some have considerably restricted their diet by the time they consult. The patient's beliefs may have either a rational or emotional basis. The evidence that the gut is in some way sensitive to particular foods is limited. Food is chemically highly complex and response to food exclusion is poorly reproducible, leading desperate patients to more and more restricted and illogical diets. Such circumstances make patients easy prey to unscrupulous practitioners and there are many "fringe" practitioners benefiting from the confusion.

Studies that have used dietary restriction followed by sequential introduction of single foods have reported specific food intolerance in 33-66% of IBS patients.^94 95 The commonest intolerance reported in the UK is to wheat, followed by dairy products, especially cheese, yoghurt and milk, coffee, potatos, corn, onions, beef, oats, and white wine.⁹⁴ Ingestion of osmotically active, poorly absorbed fermentable carbohydrates such as lactulose is known to cause typical IBS symptoms such as bloating, cramps, and diarrhoea. A recent study showed increased colonic hydrogen production in IBS. An exclusion diet was reported to reduce both symptoms and gas production in response to a standard dose of lactulose implying that the diet modified the fermentation capabilities of colonic bacteria.⁹⁶ The indirect nature of this response to diet may explain why the clinical benefit varies as the bacterial flora is itself so variable.

Adult acquired hypolactasia is common in the UK, with an incidence of 10% in those of Northern European descent, rising to 60% in Asians, and 90% in Chinese patients. Regional differences in dairy intake may account for the variable benefit reported with lactose free diets in IBS. Thus in Denmark, with a traditionally high intake of dairy products, a low lactose diet has been reported to produce improvement in 13 of 20 Danish adults with symptoms of IBS and objective evidence of lactose malabsorption.⁹⁷ However, only subjects ingesting a substantial amount of lactose (equivalent to more than 0.5 pint of milk per day) can expect to benefit from lactose restriction as lower amounts do not cause symptoms, even in lactose malabsorbers.⁹⁸

An initial study using elimination diets (that is, diets that eliminate all but a single fruit, meat, vegetable, etc) improved symptoms in 67% of those who completed the study. More practicable exclusion diets, which make less demands on the patient, have been developed which only exclude foods that had commonly been implicated in food intolerance from the earlier studies (for example, wheat, milk, coffee, potatos, corn, onion, beef, oats, cheese, and white wine). Such studies had a lower success rate (48.2-50%) with similar compliance rates.

The validity of these studies of food intolerance is hard to evaluate as a placebo response cannot be excluded unless a double blind food challenge is performed. Such studies, which involve blind challenge with blended foods passed down nasogastric tubes, bypass the important social, psychological, and physical aspects of eating, which are likely to be at least as important as the direct effects of individual food constituents on the gut. They are really only valid in identifying food allergy as the relatively small amounts of material instilled are not enough to elicit symptoms in cases of food intolerance. An early study using nasogastric delivery of suspected food reported six of 25 consecutive IBS patients who correctly identified food triggers and showed an increase in prostaglandins in rectal dialysate.⁹⁵ However, a subsequent study of 13 patients who had identified a food intolerance by means of an exclusion diet found a high placebo response with only three patients showing a significant ability to identify food triggers when administered double blind.⁹⁹

True food allergy is much less common and usually not difficult to recognise if food ingestion is associated with urticaria, asthma, eczema, angioedema, and rhinorrhoea with a high incidence (70%) of positive skin prick or high RAST scores.¹⁰⁰ Such patients usually see an immunologist rather than a gastroenterologist and are not usually thought to have IBS. When symptoms were purely gastroenterological, only 15 of 88 who believed they were allergic actually had their perceptions confirmed by double blind trial.¹⁰¹ It is worth noting that those who respond immediately to food ingestion are more likely to have positive skin tests than those who report symptoms which come on some hours after food ingestion.¹⁰² Positive skin prick testing for common food antigens has been reported in up to a third of patients with IBS and these patients have been reported to respond better to elimination diet and type I hypersensitivity inhibitors such as sodium cromoglycate.¹⁰³ These results need confirming before definitive conclusions can be drawn.¹⁰⁴ It should be recognised that in only a minority of cases is the patient's beliefs confirmed objectively, so some of their response must be psychologically determined. Recent studies showing that mast cell degranulation can be psychologically triggered¹⁰⁵ together with evidence that food allergy patients degranulate jejunal mast cells in response to cold stress¹⁰⁶ open the way for a possible explanation whereby stress or patient's beliefs about food might trigger a gastrointestinal response.

	6.0 Diagnosis

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Functional gastroenterological disorders are common but only about half actually consult their general practitioner¹⁰⁷ and of these only about one in five are referred to a hospital consultant in any given year. Most assessment and management is therefore carried out in general practice. Unfortunately, most published evidence relates to patients referred to hospital.

6.1 DIAGNOSIS AND MANAGEMENT IN GENERAL PRACTICE
A careful and detailed history, often accrued over several short interviews and sometimes over many months or even years, is required. This will take account of psychological factors, past family and personal history, as well as the social circumstances of the patient, which the general practitioner is uniquely placed to assess. The patient aged less than 45 years who describes typical symptoms (fig 1) without sinister features, such as weight loss, rectal bleeding or symptoms responsible for night time waking, probably has FGD. This should be supported by a normal physical examination including, where relevant, rectal examination and no evidence of anaemia. The diagnosis is more likely if the patient is female, has a history of greater than two years, and has attended frequently in the past with non-gastrointestinal symptoms such as malaise and backache. If symptoms are typical then no further investigations are necessary to establish a working diagnosis. However, if there are atypical features or the history is short, it may be appropriate to perform some of the screening tests referred to below.

View larger version (33K): [in this window] [in a new window]   Figure 1   Stages in the evaluation of the irritable bowel syndrome (IBS).

A typical history with or without negative test results should lead to a firm diagnosis with detailed explanation and reassurance, preferably without new medication, followed by further review if symptoms continue. Simple pharmacological or dietary interventions may be appropriate for some patients at that time. Most symptoms will resolve, or remain unchanged but acceptable, and need no further attention.

6.2 WHEN TO REFER
Patients presenting for the first time in later life and those with atypical symptoms normally warrant hospital referral. However, some patients in whom the general practitioner has made a confident diagnosis of FGD develop further symptoms or worsening anxiety, often related to adverse life events such as bereavement or separation.²⁸ These patients also warrant referral to help exclude an alternative diagnosis and to provide more definitive reassurance than the primary care physician can offer. The general practitioner is well placed to understand the illness in the wider context of the patient's life, and it is important that this information is transmitted frankly and comprehensively to specialists when referral is needed. The skilled general practitioner will recognise that these patients commonly have complaints relating to several systems, and will avoid the fragmentation of care that so easily occurs if every new complaint results in referral to a different specialist.

6.3 DIAGNOSIS IN HOSPITAL SETTING
Although functional disorders account for 36-50% of all outpatient consultations, the filtering process means that the incidence of other diseases is higher than in general practice and therefore further investigations are often indicated.

Symptom criteria such as those devised by Manning differentiate IBS reasonably well from normal subjects or patients with peptic ulcer or reflux^7 31 but do not reliably distinguish IBS from inflammatory bowel disease.^108-110 Thus symptoms alone cannot be relied upon but must be augmented by physical examination, demographic data such as age and sex, together with the progression of symptoms over time, all of which strongly influence the a priori probability of the different diseases from which IBS must be distinguished. The most important diagnosis not to be missed is cancer and as age and family history are the main risk factors, these will have a strong influence in deciding who to investigate.

A careful dietary and drug history is vital to identify unusual dietary habits or new medications whose use may have preceded the development of symptoms. Particular attention should be given to low/excess intake of dietary fibre, or excess of poorly absorbed sugars such as fructose or sorbitol or stimulants such as coffee or tea. Similarly, a wide range of drugs can cause bowel disturbance with diarrhoea and/or abdominal discomfort, such as angiotensin inhibitors,  blockers, antibiotics, chemotherapeutic agents, proton pump inhibitors, or NSAIDs, while constipation may be related to opiate analgesics, calcium channel blockers, or antidepressants with anticholinergic effects, to mention just a few. Although it is common to find a positive family history of IBS this is not unexpected in so common a condition and no study has shown this to be of any diagnostic help.

Patients with conventional IBS symptoms such as those described by Manning, or those that fulfil the Rome I criteria who have no alarm symptoms and no abnormal findings on physical examination in the hospital setting have a 52-74% chance of having IBS.^31 111 Non-gastroenterological features such as lethargy, poor sleep, fibromyalgia, backache, frequency and urgency of micturition, nocturia, incomplete bladder emptying, an unpleasant taste in the mouth, early satiety, and dyspareunia are all commoner in IBS than controls and supportive of the diagnosis.^112-114 Many authors have drawn attention to the striking disparity between the proclaimed severity of symptoms and patient's desperation with their otherwise healthy appearance. Phrases like " symptoms ruling my life", " desperation", "you must do something" will strike a cord with many experienced practitioners.

Although as already indicated, abnormal levels of anxiety, depression, and somatisation are features of many patients who are referred to hospital, these features do not discriminate between IBS and other GI diseases.³⁰ Inquiring about these emotionally disturbing features is usually inappropriate at the first visit but may be worth exploring when initial tests are unrewarding.

Although specificity of diagnosis after a history and physical examination has been reported to be improved to over 95% by using a scoring system that includes full blood count (FBC) and erythrocyte sedimentation rate (ESR),¹¹⁵ others have not found such good discrimination.¹¹⁶ Sigmoidoscopy, which can be done at the first clinic visit, should exclude those with ulcerative colitis or rectal cancer. If the rectum appears macroscopically normal, routine rectal biopsy does not usually add anything.¹¹⁷ However, in those with diarrhoea as a major complaint, it should be performed as it may provide evidence of microscopic colitis which may alter management significantly.¹¹⁸

6.4 FURTHER INVESTIGATIONS
How many further investigations beyond a simple blood count are performed depends on what is considered to be an acceptable level of missed diagnoses. A "screen" including thyroid function, stool microscopy for ova, cysts, parasites and fat globules, and flexible sigmoidoscopy with colonic biopsy, together with lactose tolerance testing in a large (1452 patients) American study of patients fitting IBS criteria gave a yield of 6% thyroid abnormalities (3% hyperthyroid, 3% hypothyroid), occult inflammatory bowel disease in 1%, and evidence of lactose malabsorption in 21-25%.¹¹⁹ Patient reports of lactose intolerance relate poorly to objective evidence of lactose malabsorption and cannot be relied upon.¹²⁰ It would therefore be logical to perform a breath hydrogen test for lactose malabsorption on IBS patients who are regular consumers of more than 0.5 pint (280 ml) of milk or equivalent dairy products, especially if they come from a racial group with a high incidence of lactose malabsorption. Alternatively, the response to lactose exclusion may be helpful although the result is usually less clear cut than the breath hydrogen test. Other simple screening tests which are logical include ESR, calcium and albumin, and antiendomysial antibodies, but there is no published evidence as to their yield, which is likely to be low (1-2%). However, it should be borne in mind that cheap tests with a low yield may yet be cost effective.

Patients with high stool weight (>200 g daily) should have a laxative screen, which in some series is positive in about 15-26% of such cases.^121 122

6.5 IMAGING
Colonic cancer is not reliably excluded¹¹⁰ by history, and patients with a positive family history or who are older than 45 years at symptom onset (when the incidence of sporadic colon cancer begins to rise steeply) should be considered for either a barium enema or colonoscopy. Ultrasound rarely detects a relevant alternative diagnosis in patients with suspected IBS and is not recommended as it uncovers coincidental asymptomatic abnormalities such as gall stones and fibroids in 8%.¹²³ This may easily lead to inappropriate surgery with no benefit to symptoms. Small bowel Crohn's disease in its early stages is easily confused with IBS and barium follow through should be considered for patients with worsening symptoms or suspicion of an abdominal mass, particularly if there is anaemia or elevation of ESR or C reactive protein. However, it should be remembered that this examination exposes the ovaries to appreciable radiation and it should be used sparingly in young females.

6.6 FUNCTIONAL TESTS
Various measures of gut function, including bile acid absorption (SeHCAT seven day retention) and gut transit have been shown to be abnormal in functional diarrhoea but are not widely used in typical IBS. One study reported that five of 42 patients with functional diarrhoea retained <8% SeHCAT and responded to cholestyramine.¹²⁴ More recently, patients with unexplained diarrhoea and stool weights >200 g were shown to have reduced bile acid retention.¹²⁵ Ileal and colonic biopsies have yielded inconsistent results and at present it seems likely that low retention in most cases is non-specifically related to fast small bowel transit.¹²⁶ Rare isolated defects in bile salt absorption have been described¹²⁷ but are unlikely to be responsible for more than a very few cases of IBS.

6.7 PROGNOSIS
Once the diagnosis is established the incidence of new significant diagnoses is extremely low. Harvey et al found no significant new diagnoses in 104 patients followed for five years, the diagnosis being largely based on symptoms, as only 12% of these had radiological studies.⁸⁹ Another study of 112 patients in which the majority had extensive radiological studies reported only two initial misdiagnoses of IBS (one chronic pancreatitis and one carcinoma of the pancreas). Five years later one case of thyrotoxicosis and one of gall stones had become apparent, values probably no different from the expected incidence of disease in initially healthy controls over a five year period. Thus the chance of remaining free of serious disease in IBS is excellent.

The prognosis for continuing abdominal symptoms is however less good and depends on the criteria used, with about 30% still symptomatic at five years in Harvey's study⁸⁹ but only 5% of patients completely symptom free in a Danish five year follow up study.¹⁴ Symptoms vary both in severity and quality with time. Thus a substantial proportion of individuals with IBS symptoms in the community experience loss of IBS symptoms over 12 months but may develop other functional symptoms such as FD.³ Factors that have been shown to worsen prognosis include more prominent psychological symptoms⁸⁸ and a longer history of illness²⁴ as well as previous abdominal surgery.¹²⁸

	7.0 Management and treatment

Top 1.0 Preface 2.0 Summary 3.0 Spectrum of functional... 4.0 Epidemiology 5.0 Aetiology 6.0 Diagnosis 7.0 Management and treatment 8.0 Pharmacological treatments 9.0 Cost effectiveness Management guide for IBS:... 10.0 Appendix References

Most of this will be carried out in general practice (fig 1). The mainstay is explanation and reassurance in terms that the patient can understand, together with sensible lifestyle adjustments relating to diet, medications, and stressors, which appear to precipitate symptoms.

7.1 POSITIVE DIAGNOSIS AND EXPLANATION
Making a definite diagnosis helps both doctor and patient by reassuring them that it is unlikely that another alternative diagnosis will emerge over the ensuing years.⁸⁹ However, this not does make the symptoms disappear and the patient may continue to need a supportive understanding relationship with a physician.

7.2 LISTENING TO THE PATIENT
Simply listening to the patient and accepting that their symptoms are real and valid may help, especially if previous consultations have been unsatisfactory. It is important to ask the patient about their fears and beliefs. A high proportion believe there is some serious disease, in particular cancer. The condition needs to be explained simply using analogies with which a layman can relate. Cramps and spasms are easily accepted as causes of pain. Most can understand how anxiety, such as before a test or examination, can cause diarrhoea. This can be used to introduce the idea of brain-gut interactions. Explanation of possible mechanisms such as "sensitive gut" or reaction to infection, if put in simple terms, reduces anxiety caused by unexplained symptoms and is usually highly valued by the patient. At a minimum, this prevents further unnecessary referrals and possibly hazardous treatments, such as hysterectomy or cholecystectomy. Although accepted by many clinicians, these concepts have not been subjected to proper randomised controlled trials.

7.3 LIFESTYLE ADVICE
This will be much more important at first presentation in primary care than in hospital practice, when most will already have tried and failed such measures. This will include a careful dietary and lifestyle history, identifying food fads or deficiencies, including excess or lack of dietary fibre. Lack of exercise and not allowing adequate and suitable time for regular defecation are common problems which are especially relevant to constipated IBS sufferers. Keeping a two week diary of symptoms, stresses, and dietary intake may identify aggravating factors and will be helpful in discussing management. Those with constipation/diarrhoea need advice about intake of "fibre" or poorly absorbed non-starch polysaccharides, fructose, sorbitol or lactose, which may be either increased or decreased with benefit. Intake of drugs and herbal medicines, which may affect the bowels, should also be noted.

7.4 PLACEBO RESPONSE
Defining the best treatment in IBS has been difficult, at least in part because the placebo response is so marked, averaging 47% in a recent survey of 25 randomised controlled drug trials. This effect was approximately three times larger than the additional drug effect, which was 16%.^129-132 However, the longer the follow up the smaller the placebo effect becomes and as yet long term benefit has only been shown for psychological and dietary treatments. The high placebo response during clinical trials may reflect the effect of the greater contact between the patient and health care professionals. Compared with routine outpatient clinics, much more time is available for explanation, reassurance, and general discussion. The value of reassurance in IBS has not been studied systematically but in FD the patients' responses to reassurance that they do not have serious disease depends on psychological factors. Thus while patients with low or moderate anxiety do well with the reassurance provided by negative endoscopy, the benefit to those with marked anxiety is short lived.¹³³ These patients, whose quality of life remains poor despite reassurance and explanation and in whom psychological features appear prominent, may respond to more formal psychological treatments. Several forms of therapy have been studied in IBS but studies which have not used a suitable placebo are difficult to interpret as in the short term at least, any form of increased patient contact has a non-specific beneficial impact.¹³⁴

7.5 DIETARY FACTORS
Many patients believe that some dietary item is responsible for symptoms and some have adopted inappropriately restrictive diets. Equally, some patients have excessively large intakes of indigestible carbohydrate, fruits or caffeine, and these patients may benefit from simple dietary advice. Others, particularly patients of non-European descent, may have hypolactasia. Those with a substantial intake of lactose (>0.5 pint (280 ml) milk/day) may benefit from a low lactose diet. Rarely, excessive intake of fructose may cause symptoms due to slow or incomplete absorption which could cause gut distension to which IBS patients appear especially sensitive.¹³⁵ Bloating is an extremely common symptom in the normal population, being