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REVIEW ARTICLE Table of Contents   
Year : 1998  |  Volume : 4  |  Issue : 3  |  Page : 138-146
The irritable bowel syndrome


Department of Internal Medicine, Gastroenterology Division, University Hospital Gasthuisberg, Belgium

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Date of Submission21-Feb-1998
Date of Acceptance08-Mar-1998
 

How to cite this article:
Vaerenbergh WV, Tack J. The irritable bowel syndrome. Saudi J Gastroenterol 1998;4:138-46

How to cite this URL:
Vaerenbergh WV, Tack J. The irritable bowel syndrome. Saudi J Gastroenterol [serial online] 1998 [cited 2019 Nov 13];4:138-46. Available from: http://www.saudijgastro.com/text.asp?1998/4/3/138/33908


Functional bowel disorders such as noncardiac chest pain, nonulcer dyspepsia, and the irritable bowel syndrome share the symptoms of chronic discomfort or pain, attributed to the gastrointestinal tract, usually with a variety of other symptoms. Since no histological, biochemical, or physiological abnormality has been identified that could consistently explain the patients' respective prevalent symptoms, these syndromes have been referred to as "functional" as opposed to "organic" disease and so on[1]

Functional bowel disorders may be characterized by symptoms that are attributable to the pharynx, esophagus, stomach, biliary tract, small intestine, colon or the anorectum [Table - 1]. In the irritable bowel syndrome, symptoms refer mainly to the colon.


   Symptoms Top


The irritable bowel syndrome is characterized by a symptom cluster which includes abdominal pain, often relieved by defecation, distention of the abdomen, a disordered bowel habit, a frequent feeling of incomplete evacuation, mucus in the stool, looser stools with the onset of pain, and more frequent stools with the onset of pain. In addition, a number of non-colonic features have also been recognized, including nausea, vomiting, early satiety, nocturia, frequency and urgency of micturition, incomplete bladder emptying and fatigue.


   Definition Top


At present the definition of the irritable bowel syndrome according to the 'Rome symptom criteria' has gained international acceptance, at least for application in research and in clinical trials (1). According to this definition, the irritable bowel syndrome consists of continuous or intermittent symptoms of abdominal pain or discomfort, accompanied by at least three of the following criteria: pain relieved with defecation or flatus, altered stool frequency in at least 25% of occasions, altered stool consistency in at least 25% of occasions (hard, loose or watery), altered stool passage of stools in at least 25% of occasions (feeling of incomplete rectal evacuation, difficult passage of stools or urgency), abdominal bloating, or mucus in the stools. The Rome criteria have only a limited usefulness in clinical practice. Only after exclusion of organic diseases, they can be helpful in making the diagnosis of the irritable bowel syndrome.


   Epidemiology Top


The irritable bowel syndrome is one of the most frequent conditions that physicians are confronted with: 40 to 70% of the patients attending a gastroenterological clinic in the civilized world will have a functional disorder. Population studies have shown that 17 to 21 % of a western population will have symptoms that are compatible with the irritable bowel syndrome. The vast majority of these will not consult a physician [2],[3],[4],[5]. Economic and cultural factors will influence the distribution of people with irritable bowel symptoms that will seek medical care. Medical attention will mainly be sought by women, who constitute 75 to 80% of the patients.

The irritable bowel syndrome seems to be frequent in China, less frequent in South-East Asia, and more frequent in the male population of India. The prevalence of the irritable bowel syndrome decreases with age and with a higher income. There is no significant association with race, size of the family, geographical region, population density or employment status.

The irritable bowel syndrome can be influenced by psychosocial factors, such as familial or cultural attitude towards disease and adverse life events, psychological background, individual coping strength and social support. These factors will influence the use of medication and seeking of medical attention. Although these factors do not seem to be directly linked to the etiology or the pathophysiology of the irritable bowel syndrome, they are relevant in understanding the attitude of the patient towards his symptoms, and in planning a therapeutic strategy.


   Impact of the Irritable Bowel Syndrome Top


The morbidity and life expectancy in patients with irritable bowel syndrome does not differ from that in the general population [6], but a considerable impact on daily life is present. Patients with the irritable bowel syndrome experience symptoms that interfere with normal daily activities, for which they repeatedly see physicians, and they have a higher number of days absent from work or school[7]. Direct medical costs in patients with the irritable bowel syndrome are significantly higher than those in a control population[8]

Pathogenesis of the Irritable Bowel Syndrome

The etiology of the irritable bowel syndrome remains unclear. Most likely, it is caused by the convergence of a number of different factors in individuals with a certain predisposition.

Psychosocial factors

Psychosocial factors in the irritable bowel syndrome relate to a number of topics that have received variable attention in the past. Initial studies were focused at detecting specific personality traits in patients with the irritable bowel syndrome. Later, the focus was put on illness behavior and health-seeking behavior. More recently, life events and sexual or physical abuse have received more attention.

The irritable bowel syndrome is often considered a somatization syndrome, reflecting underlying psychopathology. Patients with the irritable bowel syndrome have more psychological disturbances than the general population, but less than psychiatric outpatients[9]. Depending on the type of testing used, the prevalence of certain psychological and psychiatric disturbances is higher in patients with the irritable bowel syndrome[10],[11] However, the psychological disorders in patients with the irritable bowel syndrome are non-specific, and, according to some studies, their prevalence might be comparable in patients with benign gastrointestinal disorders. These data suggest that psychoneurotic disorders in the irritable bowel syndrome might be secondary components, rather than the cause of symptoms[12],[3].

The observation that only a minority of persons with symptoms suggestive of the irritable bowel syndrome is seeing a physician, led to the hypothesis that psychopathology might not determine the symptoms, but rather who would come to medical attention for them. Comparative studies demonstrated that those subjects with functional bowel symptoms who see a physician are more focused on their symptoms, might be indicative of illness behavior[2],[14],[15],[16]. Sex differences in seeking medical attention might explain why the irritable bowel syndrome is more frequent in women, although hormonal factors might also play an important role[17],[18]

Patients with irritable bowel syndrome experience more than asymptomatic controls[19],[20], and patients often experience a temporal relationship between stress and symptoms. Stressful life events do not only precipitate symptoms in the irritable bowel syndrome, but also in several psychosomatic and somatic disorders. Well-controlled studies are lacking unfortunately, and in a prospective study, a correlation with stress could only be found in 25% of the exacerbations of irritable bowel symptoms[21]. Moreover, about half of a healthy population experiences that stress may alter bowel habits and induce abdominal pain[2]. Hence, the notion that the irritable bowel syndrome might be stress-induced is far from proven, and may even be hampered by over-emphasizing of stressful events when retrospectively seeking a cause or explanation. A possible underlying mechanism is also unclear: whereas the irritable bowel syndrome is a chronic disorder, and stressful life events are often having a chronic impact, only acute stress has been studied experimentally. Moreover, experiments using acute stress have generally failed to elicit typical irritable bowel syndrome symptoms.

Recently, several groups have reported a higher prevalence of sexual or physical abuse in patients with functional bowel disorders[1],[8]. However, the prevalence is already high in asymptomatic subjects in the general population[22], thus questioning the specificity of this observation.

Sleep disorders

Sleep disorders are frequently observed in patients with the irritable bowel syndrome[23] and, in healthy volunteers, sleep deprivation is able to elicit irritable bowel-like symptoms[24].

Infection and inflammation

In a large retrospective study, Chaudhary and Truelove demonstrated that in about one third of patients with irritable bowel syndrome, symptoms seemed to have started after a gastrointestinal infection[25]. Moreover, the prevalence of irritable bowel symptoms in patients with ulcerative colitis in remission seems to be abnormally high[26]. These and other observations are the basis of the hypothesis that inflammation might predispose to the development of the irritable bowel syndrome[27]. Animal studies were indeed able to demonstrate that inflammation is inducing persistent neuromuscular dysfunction in the gastrointestinal tract. The mechanisms that underlie this phenomenon are currently being studied. It is already clear that a large array of inflammatory mediators, including cytokines and arachidonic acid metabolites, are able to alter neuromuscular function.

Convergence of inflammation and psychological factors

A group of patients with proven  Salmonella More Details enteritis were followed prospectively during several months. After two years, 32% of them had symptoms of the irritable bowel syndrome[28]. Those patients who developed irritable bowel syndrome after a Salmonella infection seemed to have more psychological disturbances, and they experienced more stressful life events during the months preceding the infection[29]. Nevertheless, the lamina propria cell count and the changes in rectal sensor and motor function did not differ between those who did and those who did not develop a post-infectious irritable bowel syndrome. These findings suggest that psychological factors can determine the response to inflammation and the clinical expression of altered gastrointestinal function.

Pathophysiology of the Irritable Bowel Syndrome

Historically, several hypotheses have been suggested to underlie symptoms in the irritable bowel syndrome. For the past decades, symptoms in functional bowel disorders have mainly been viewed as expressions of altered motor function of the gut. In most reviews, functional bowel disorders are referred to as gastrointestinal motility disorders.

Based on this theory, the prevailing therapeutic approach involves antispasmodics, bulk-forming agents and prokinetic compounds.

Intestinal motility disorders

The periodicity of the migrating motor complex is shorter in diarrhea-predominant patients than in constipation-predominant or control groups, particularly because of a shorter cycle length during the daytime[30]. Ileal propulsive waves and clusters of jejunal contractions are also more common in patients with IBS. In response to an intraduodenal infusion of a fatty meal, a correlation was observed between the presence of prolonged propagated contractions and cramping discomfort or pain[31]

Colonic motility disorders

In response to step distention of the rectosigmoid, slow colonic contractions lasting>15 seconds and occurring at irregular intervals were more frequently encountered in patients with IBS than in normal subjects. Durations of > 15 seconds were more frequent in the diarrhea-predominant group. The colonic motility index was correlated with the severity of bowel symptoms in diarrhea predominant, but not constipation-predominant patients[18]

The diarrhea-predominant group had a lower rectal compliance than constipated patients with IBS or controls. The reflex relaxation of the internal anal sphincter induced by rectal distention was less sensitive in the constipation-predominant group[32].

Visceral hypersensitivity

About 20 years ago, Ritchie showed that in patients with the irritable bowel syndrome, the distention volume required to induce pain from the pelvic colon was on average, lower than in controls[33]. Visceral thresholds for discomfort and pain in response to isovolumic distention of the colon are lower in IBS patients than in controls. This anomaly is not due to a defective compliance since compliance curves and basal colonic tone were similar in both groups. Consequently, colonic wall resistance does not account for these abnormal sensory thresholds in IBS. Similar findings have been reported previously in the stomach in patients with functional dyspepsia, in the esophagus of patients with noncardiac chest pain and in the rectosigmoid in patients with the irritable bowel syndrome. Somatic sensitivity is not enhanced in patients with the irritable bowel syndrome[34]

In the past five years, the "colonic hyperalgesia hypothesis" has undergone a resurgence with several well-controlled studies showing a reduction in the threshold pressure or volume of colorectal distention required to induce perception or a sensation of discomfort or pain in patients with IBS[18],[32]. It is unclear whether the same pathways are involved in the encoding of discomfort and pain (response to noxious stimulation, specificity theory versus intensity theory). Recent studies evaluating mechanical and electrical stimulation of intestinal afferents in the irritable bowel syndrome, concluded that patients with the irritable bowel syndrome have selective hypersensitivity of mechanical afferents[35]

Lembo et al. attempted to characterize indirectly the receptors involved in signaling colorectal sensation by using two types of balloon inflation: phasic and ramp[36]. Plourde et al., who used intrarectal lidocaine, concluded that during slow ramp inflation, rapidly adapting mucosal afferents will be activated by friction of the balloon with the mucosa, whereas the activation of the muscle mechanoreceptors will be limited by reflex relaxation of the muscle[37]. From the study of Lembo et al., it is clear that phasic distention is the stimulus to use when investigating hypersensitivity in patients with IBS. Also, the pattern of viscerosomatic referral differed from controls. Lidocaine did not affect the threshold for sensory response in patients with IBS, suggesting that mucosal afferents are not the predominant source of the colorectal hypersensitivity in IBS, although they do contribute to the sensory response in controls. This suggests that in IBS, the receptors that become sensitized, are high-threshold mechanoreceptors located in the muscle or perhaps in the serosa.

However, not all patients with IBS have a hypersensitive rectum. The observation of an apparent hypersensitive subgroup of patients with IBS could result from variation in the regional manifestation of hypersensitivity, temporal variation in sensitivity or variation in sensitivity depending on the type of stimulus (electrical, slow ramp and phasic balloon distention).


   Treatment Top


General measures

In the literature, several therapeutic trials in the irritable bowel syndrome have been reported. The patient selection for participation differs strongly between studies. Moreover, many studies assess vague criteria, like "overall improvement". Hence, the number of adequate placebo-controlled trials is limited. These trials report a major placebo effect in the irritable bowel syndrome. The magnitude of the placebo effect differs between symptoms: 50 to 70% for abdominal pain, and 30% for diarrhea. Studies which are not placebo-controlled are of little value in the irritable bowel syndrome. Pharmacotherapy of the irritable bowel syndrome is best directed towards specific symptoms, with the aim of modulating intestinal motility, visceral sensitivity or associated psychiatric disturbances.

Therapy for the irritable bowel syndrome does not only consist of pharmacological treatment but also of supportive measures. Once the diagnosis of irritable bowel syndrome has been made (after the initial examinations and exclusion of organic pathology), the patient should be reassured (with emphasis on the absence of severe organic pathology) and extensively informed about the nature of his complaints. An empathic approach is very important.

Dietary measures like fiber supplements or bulk forming agents (e.g. psyllium or ispaghula) can be used in constipation-predominant irritable bowel syndrome : they have a significant beneficial effect on constipation, but they seem no better than placebo concerning other complaints (abdominal pain, bloating, diarrhea, frequency of stools). In case of diarrhea-predominant irritable bowel syndrome, one should bare in mind the possibility of an associated carbohydrate intolerance; a restricted intake of carbohydrates may alleviate the severity of irritable bowel symptoms.

Dietary measures

In diarrhea-predominant irritable bowel syndrome, an underlying carbohydrate intolerance (lactose, sucrose, sorbitol or fructose intolerance) or the existence of a food allergy has to be considered. No studies have demonstrated that carbohydrate intolerance can be the sole cause of typical irritable bowel symptoms, but reducing the intake of carbohydrates can improve symptoms[38]. A therapeutic trial with a diet eliminating those carbohydrates can be considered.

In constipated patients, a diet rich in fiber may improve symptoms, while diarrhea can worsen. Increasing the fiber content of the diet is best done gradually. However, overall the therapeutic impact of a diet rich in fiber is rather disappointing[39]

Fiber supplements

Fiber supplements are traditionally prescribed to patients with constipation-predominant irritable bowel syndrome, and they may improve constipation. The effect of fiber supplements on stool frequency and stool weight are determined more by psychometric variables than by the type or the quantity of the administered fiber[40]. For alleviating abdominal pain, fiber is not superior to placebo[41], and there is often an adverse influence on symptoms of abdominal pain, bloating or diarrhea. Alternatively, bulking agents like psyllium or ispaghula can be prescribed, but their efficacy has not been proven[42],[43]

Antispasmodics

They cause relaxation of the intestinal smooth muscle cells, mostly by inhibiting the influx of calcium. Placebo-controlled studies show an inconsistent effect : some show a good effect on complaints like abdominal pain and varying bowel habits[44], others show no significant improvement of diarrhea or constipation [45]

Anticholinergics

Anticholinergics inhibit basal as well as meal induced gastrointestinal motility by blocking muscarine M 2 -receptors on the intestinal smooth muscle. In comparison with the impact on motility, the clinical effects of anticholinergics are rather small : in the short term they may improve abdominal pain and rectal urgency, but they often cause systemic anticholinergic side effects; an effect in the long term has not been proven[48]

Opioids

Opioids that do not cross the blood-brain barrier (e.g. loperamide) exert their action via mu-receptors on the enteric nervous system, by enhancing non-propulsive motility and inhibiting propulsive motility. They slow the intestinal transit, inhibit intestinal secretions, inhibit rectal sensitivity and increase the internal anal sphincter tone. Placebo-controlled trials confirmed the effect of loperamide on diarrhea, rectal urgency and abdominal pain in the irritable bowel syndrome[47],[48]

Fedotozine is a peripheral acting kappa opiate receptor agonist that decreases visceral sensitivity. Studies in patients with the irritable bowel syndrome showed a significant improvement of abdominal pain[49]

5-HT3 antagonists

5-HT3 receptors are thought to be involved in the regulation of gastrointestinal motor function and in the modulation of visceral sensory function. In a randomized, double-blind cross-over placebo controlled study of ondansetron 16 mg tid, patients with IBS experienced significantly fewer daily episodes of pain while on ondansetron[50] Ondansetron caused firmer bowel movements. Studies investigating the effect of 5-HT3 antagonists on rectal sensitivity have yielded conflicting results. Granisetron, but not ondansetron or alosetron, decrease the sensitivity to rectal distention in patients with the irritable bowel syndrome[51],[52]

Tricyclic antidepressants

In low dose (e.g. desipramine 150 mg/day, or trimipramine 50 mg/day), tricyclic antidepressants improve abdominal pain, although they may induce constipation[54],[55]. It's unclear whether they act by influencing the mood, through a central analgetic effect, or a peripheral anticholinergic or serotonin effect, although the effect on the mood seems predominant [56]. The potential role of selective 5-HT reuptake inhibitors has not been studied systematically.

Miscellaneous

Tranquilizers improve 'general well-being' without influencing specific symptoms like abdominal pain, distention or bowel habits. Prokinetic (e.g. domperidone) are no better than placebo, concerning the effect on abdominal pain, constipation, diarrhea or low abdominal bloating. In a randomized, double-blind, placebo-controlled study in constipation predominant irritable bowel syndrome, cisapride significantly reduced abdominal pain, bloating and flatulence[57]

Psychotherapy

Because of the rather disappointing effects of standard medical treatment of the irritable bowel syndrome, and because of the association with psychological disturbances, several forms of psychotherapy have been applied. Rare controlled trials have investigated dynamic psychotherapy, relaxation therapy, cognitive behavioural therapy and hypnotherapy.

The application of dynamic psychotherapy, in addition to classical medical therapy, significantly increases therapeutic benefit, both for physical and for psychological symptoms[58],[59] Only one controlled trial used relaxation therapy, showing that relaxation therapy was superior to a placebo treatment[60]. Cognitive therapy is superior to an equivalent time of therapeutic contact not involving cognitive therapy, both for physical and for psychological symptoms[61],[62]. In a controlled trial, hypnotherapy was better than supportive therapy and placebo medication in a group of refractory irritable bowel syndrome patients for improving symptoms of abdominal pain and diarrhea [63],[64].. Additional studies showed that hypnotherapy decreases rectal sensitivity to distension[32].

In spite of these studies, the role of psychotherapy in the irritable bowel syndrome remains unclear. The studies have used different criteria for patients selection, and different definitions of the irritable bowel syndrome. Moreover, most studies selected refractory patients, with a higher likelihood of underlying psychological disturbances, for psychotherapy. Because of these methodological problems, the value of psychotherapy still has not been proven[65].


   Prognosis Top


The irritable bowel syndrome is a chronic relapsing disorder. Although the prevalence in a community seems to be stable, there is a continuing substantial turnover of patients[5],[66]. Each year about 30% of patients will lose their symptoms, and 10% will gain new symptoms. In follow-up studies of 1 to 10 years 50-70% become virtually asymptomatic, and about one third will experience persistent symptoms.

It's unclear whether the prognosis differs for diarrhea-predominant or for constipation ­predominant irritable bowel syndrome. The prognosis seems to be better in patients with intermittent complaints than in those experiencing continuous abdominal pain. The prognosis also seems to be better in patients who have no major psychiatric disturbance.

The diagnosis of irritable bowel syndrome is a safe diagnosis in young patients: in less than 5% the diagnosis is changed in a follow-up period of 1 upto 5 years[67],[68]

 
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49.Dapoigny, M., Abitbol, J.L., and Fraitag, B. (1995). Efficacy of the peripheral kappa agonist fedotozine versus placebo in the treatment of the irritable bowel syndrome: a multicenter dose-response study. Dig. Dis. Sci.  Back to cited text no. 49    
50.Steadman, C.J., Talley, N.J., Phillips, S.F., and Zinsmeister, A.R. Selective 5-hydroxytryptamine type 3 receptor antagonism with ondansetron as treatment for diarrhea-­predominant irritable bowel syndrome: a pilot study. Mayo Clinic Proceedings 1992;67:732-8.  Back to cited text no. 50    
51.Prior, JA., and Read, N.W. Reduction of rectal sensitivity and postprandial motility by granisetron, a 5-HT3 receptor antagonist, in patients with irritable bowel syndrome. Aliment. Pharmacol. Ther. 1993;7:175-80.  Back to cited text no. 51    
52.Hammer, J., Phillips, S.F., Talley, N.J., and Camilleri, M. Effect of a 5-HT3-antagonist (ondansetron) on rectal sensitivity and compliance in health and the irritable bowel syndrome. Aliment. Pharmacol. Ther. 1993;7:543-51.  Back to cited text no. 52    
53.Zighelboim, J., Talley, N.J., Phillips, S.F., Harmsen, W.S., and Zinsmeister, A.R. Visceral perception in irritable bowel syndrome. Rectal and gastric responses to distention and serotonin type 3 antagonism. Dig. Dis. Sci. 1995;40:819-27.  Back to cited text no. 53    
54.Greenbaum DS, et al. The effects of desipramine on irritable syndrome compared with atropine and placebo. Dig. Dis. Sci. 1987;32:257-66.  Back to cited text no. 54    
55.Clouse, R.E., Lustman, P.J., Geisman, R.A., and Alpers, D.H. Antidepressant therapy in 138 patients with the irritable syndrome: a five-year clinical experience. Aliment. Pharmacol. Therap. 1994;8:409-16.  Back to cited text no. 55    
56.Myren, J., Groth, H., Larsen, S.E., and Larsen, S. The effect of trimipramine in patients with the irritable bowel syndrome - a double-blind study. Scand. J. Gastroenterol. 1982;17:871-5.  Back to cited text no. 56    
57.Van Outryve M, Milo R, Toussaint J, et al. Prokinetic treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride. Journal of Clinical Gastroenterology 1991;13:49-57.  Back to cited text no. 57  [PUBMED]  
58.Svedlund, J., Sjodin, I., Ottoson, J.O., et al. Controlled study of psychotherapy in irritable bowel syndrome. Lance 1983;2:589-92.  Back to cited text no. 58    
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67.Holmes, K.M., and Salter, R.H. Irritable bowel syndrome - a safe diagnosis? Br. Med. J. 1982;285:1533-4.  Back to cited text no. 67    
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Correspondence Address:
Jan Tack
Department of Internal Medicine, Gastroenterology Division, University Hospital Gasthuisberg, Herestraat 49, B3000 Leuven
Belgium
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