1444
SCIENCE & PRACTICE
Pathophysiology of the irritable bowel syndrome
The irritable bowel syndrome is estimated to affect up to one-quarter of the population of western countries.! Such a common disorder should be well understood, but it is not. I will describe how research into this syndrome has changed, and I shall try to indicate how vague the notion of this condition remains.
Beginnings Mucous colitis Sir William Osler’s The Principles and Practice of Medicine, first published in 1892, contained an entry on mucous colitis, which described "... a tenacious mucus, which may be slimy and gelatinous, like frog-spawn... " passed in strings, strips, or as a continuous tubular cast of the colon. The casts were made of mucus with cell remnants and concretions called intestinal sand; colonic epithelium was normal. Patients were often hysterical, hypochondriacal, depressed, self-centred, neurasthenic, and subject to colicky abdominal pains. Some were constipated, whilst others had nervous diarrhoea. The abdomen, rarely distended, often contained a tender spot in its left upper quadrant. Hurst in 1935 agreed with Osler’s view of mucous colitis,2 describing it as a common disorder before 1914 but exceedingly rare since then. He reported that patients often brought mucus casts to his clinic and passed as much as two ounces of intestinal sand in 24 h. White showed that some cases of mucous colitis were associated with diseases such as carcinoma but like Osler he viewed this condition as a distinct clinical entity.33 Bockus, Bank, and Wilkinson described 50 cases that bore little resemblance to Osler’s mucous colitis.4 Most of their
patients were constipated, dyspeptic, depressed, introspective, exhausted, emotionally unstable, or asthenic; many had a palpable and tender colon. The findings of characteristically clear mucus and shining rectal mucosa seem normal to modem readers. Specific diagnostic criteria were unavailable and patients were identified on the basis of a history of diarrhoea, abdominal pain, and anxiety.5 Spastic colon Colonic spasm was thought to be a common feature of colitis, and was readily detectable by palpation. Ryle described 50 patients with colonic spasm6 who complained mainly of constant lower abdominal pain that became worse with anxiety, smoking, menses, and defaecation; it improved with rest, hot baths, and eating. 30% of patients had constipation, 20% had diarrhoea, and 20% had mucorrhoea. Palpation revealed the colon as a hard and tender cord. He believed that spasm reflected a disorder of autonomic nerve function. Barker identified colonic spasm and mucous colitis as the same entity,7 and speculated that autonomic nerve dysfunction was related to a specific personality disorder. mucous
Irritable colon
Jordan and Kiefer described irritable colon as a colonic musculoneural disturbance present in 30% of outpatients in a gastroenterology practice. They made the diagnosis by barium enema, noting colonic appearance, function, and the distress produced by the enema. Three symptom complexes were common: epigastric distress, nausea, and vomiting; generalised abdominal distress with belching, distension, and anorexia; and left upper quadrant distress with palpitations and heart pain. Colonic neurosis
Early writers on these conditions shared three convictions. First, that the symptoms arise from the colon; second, that the disorder is functional and not morphologically defmable; and third, that the abnormality lies in the nervous system. When they called these colonic disorders neuroses they meant autonomic nervous disorders, which were subdivided into motor, sensory, secretory, and complex. Few commentators presented any data about autonomic and enteric neuronal innervation. In the 1940s, the notion of the irritable bowel syndrome began to replace existing terms. Three essential steps in diagnosis were recommended: to identify symptoms of colonic dysfunction; to exclude organic disease of the colon, and to exclude extracolonic diseases capable of producing colonic symptoms. The principal complaint was usually of aching or cramping lower abdominal pain. Apart from the suspected autonomic disturbance, endocrinopathies and allergies were believed to have important causal roles. Neurosis now came to mean a personality disorder associated with irritable bowel syndrome rather than a primary autonomic disorder. Old science series of experiments completed over 40 years ago, Almy showed that colonic motility changed with acute stress--eg, before and after interviews focusing on emotionally charged subjects, hand immersion in ice-water, and compression of the skull with a metal band equipped with screws.9 Chaudhary and Truelove reported that they could identify predisposing psychological factors in 79% of cases of irritable bowel syndrome, this proportion being the same in patients with painless diarrhoea as in those with spastic colon.10 These factors included marital stress, anxiety over family members, sexual dysfunction, anxiety over career and finances, fear of major illness, and obsessional worrying. Hislop concluded that the syndrome was a physiological In
a
ADDRESS: Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA. Correspondence to Prof J
Christensen,
MD.
1445
concomitant of depressive disorder; 80% of his patients
improved on antidepressant therapy." Esler and Goulston found that patients with diarrhoea-predominant irritable bowel syndrome were significantly more neurotic and anxious than controls."
Interpretation of these data depends on the validity of the personality tests as well as the validity of the diagnosis of bowel disease. Uncertainty about both of these variables led to doubt about the psychosomatic cause of the syndrome. Colonic motor dysfunction
Experiments designed to show colonic motor dysfunction objectively by colonic manometry have been largely unsuccessful. There are few differences between patients with the syndrome and normal controls during manometry of the unstimulated distal colon. 13,14 After colonic stimulation by eating or by balloon distension, patients with irritable bowel syndrome showed a greater response than controls, but the test did not distinguish between diarrhoeapredominant and constipation-predominant forms of the condition.15 Trotman and Misiewicz showed that patients with the syndrome had lower colonic pressures than patients with diverticular disease and healthy controls.16 They emphasised the importance of variables such as the exact location of pressure-sensing devices, bowel preparation, and sedation. A different approach came from the study of electrical slow waves (pacemaking signals) generated in the distal colon.13 There was a disproportionate number of signals at 3/min, the usual frequency being 6/min, in patients with the irritable bowel syndrome compared with controls. The signals were buried in noise and could only be extracted by computer analysis. Although an intense debate followed about the reproducibility of these results, there has been no explanation as to how a slower than normal pacemaker rhythm could account for colon spasm.
Fig 1-Migrating motor complex in the jejunum of a normal human subject. The seven tracings show pressures recorded simultaneously from seven catheters whose open tips lay 3 cm apart. In the fasted state, the pattern varies in a 90-100 min cycle, with a period of quiescence (phase I) of about 70 min, a period of intermittent contractions (phase II) lasting about 10 min, and a period of maximum contractions (phase I 11)of about 5 min. The whole complex migrates slowly caudad. Phase II I constitutes multiple propagated contractions whose velocity exceeds that of the complex (shown by the slanting lines). Abnormal timing of these events is found in ’
diabetic enteroneuropathy, autonomic neuropathies, and the irritable bowel syndrome.
altered bowel habit.9 They found that several symptoms correlated with the failure to find organic disease: the combination of abdominal pain, flatulence, and irregularity of defaecation; symptoms lasting for more than two years; abdominal pain described as "burning, cutting, very strong, or terrible"; alternating constipation and diarrhoea; and pencil-like or pelleted stools, or mucus with stools. Other workers produced slightly different criteria .20 The International Congress of Gastroenterology has proposed a definition that takes account of these different views; it is discussed further in the next article.21 or
New science
Definition
expectation of finding clear-cut psychological and physiological correlates for the irritable bowel syndrome was naive because no concrete and uniformly accepted criteria defined the clinical syndrome. Those who had attempted to provide a definition of the syndrome had written that, although it could not be described precisely, experienced observers knew it when they saw it. The only criterion that was accepted universally was the exclusion of The
organic disease. The view about the need for
accurate
diagnostic criteria was slow to develop. For instance, Thompson collected an assortment of unexplained symptoms together under the label of "the irritable gut", thus creating a single entity out of much that remained unexplained. 17
Manning and colleagues questioned all patients referred investigation of abdominal pain, constipation, or diarrhoea.18 They inquired about 15 symptoms thought to be characteristic of the irritable bowel syndrome, which included pain related to defaecation, non-painful sensations related to defaecation, timing of defaecation, abdominal distension, and mucus discharge. The analysis revealed four symptoms that were significantly correlated to a final diagnosis of irritable bowel syndrome. These symptoms, for
called the Manning criteria, are: looser stools at the onset of pain; more frequent stools at the onset of pain; pain eased after defaecation; and visible abdominal distension. Kruis et al studied patients with abdominal pain, flatulence, now
The formulation of these symptom criteria has stimulated efforts to identify psychological or physiological correlates for the irritable bowel syndrome.
new
Psychological disturbances When patients identified by the Manning criteria are compared with healthy controls and with patients who have benign organic disease of the gut, those with the irritable bowel syndrome score higher in measures of anxiety and obsession, but not in measures of phobia, depression, somatic anxiety, and hysteria.22 Anxiety and obsession are likely to be consequences, not causes, of the symptoms. Kellow et al could not distinguish between patients with the irritable bowel syndrome and normal subjects when observing the effect of acute psychological stress on small intestinal motility. 23 Psychoneurosis as a cause of the syndrome therefore remains to be proven. This conclusion has received support from other investigators.24 However, psychosocial factors may identify health-seeking or illness behaviour.25 Motor dysfunction of the small intestine
psychological stress can alter the pattern of the migrating motor complex (fig 1), a pattern of small intestinal motility which is characteristic of fasting and is partly under the control of the central nervous system 26 In patients with the irritable bowel syndrome, such stress produced a pattern Acute
1446
Fig 2-Jejunal motility
in
a
patient
with partial obstruction of
the ileum. The seven tracings show pressures recorded from seven catheters whose tips lay 3 cm apart. The pattern, both in fed and fasted states, is one of short bursts of intense activity separated by long intervals of rest. These "clustered contractions" are also found in some patients with the irritable bowel syndrome.
of "clustered contractions", which is also found in partial intestinal obstruction (fig 2). Radiographic studies indicating altered small intestinal transit in patients with the syndrome support the notion that small intestinal motility is abnormal. 27 24 h ambulatory monitoring of small intestinal motility in patients with irritable bowel syndrome shows that the duration of the postprandial "fed pattern" of motility is shorter than in normal subjects .28 Cases with diarrhoea-predominant symptoms have abnormally brief intervals between successive migrating motor complexes in the fasted state.
Sensory abnormalities The view that irritable bowel syndrome reflects visceral hyperaesthesia has prompted several studies into the effects on pain perception of rectal distension by balloon inflation.29 Although hypersensitivity is common, the overlap with normal subjects is large. Moreover, some researchers have
been unable to find differences in the rectal pressure volume relation.3° Whitehead and colleagues have suggested altered receptor sensitivity in the rectosigmoid in patients with the irritable bowel syndrome.31
Neurological disorders Higher electromyographic activity and lower digital temperatures are found in patients doing mental arithmetic during baseline measurements and periods of calculation than in controls.32 Dinan et al gave patients and normal subjects a standard dose of desipramine and measured growth hormone release. 11of 13 patients with irritable bowel syndrome showed a blunted response, whilst no patients with peptic ulcer disease and only one normal control showed a similar result. This group concluded that abnormal central alpha-2 receptor function characterises the irritable bowel
syndrome. Comment The irritable bowel syndrome has provided physicians with a diagnostic term that can allude to almost any set of gastrointestinal symptoms that are poorly understood. Speculation and opinion led to explanations of cause in areas of knowledge that were largely unexplored (see table); for
instance, abnormalities of colonic motility when it could not be studied, autonomic and enteric nervous dysfunctions when they were not well understood, and psychoneurosis when there was no way to define it objectively. The need for a more precise definition of this syndrome has led to refinement of the criteria for symptomatic diagnosis. These new criteria focus on defaecatory dysfunction. However, there is still no clear
psychopathology or pathophysiology. The irritable bowel syndrome remains mainly a diagnosis of exclusion. Heterogeneity of pathological processes must exist in such a diagnostic category. Indeed, evidence for such heterogeneity is found if one examines the history of the syndrome. One disease after another has escaped its nosological boundaries: Crohn’s disease, lactase deficiency, lymphocytic colitis, collagenous colitis, and visceral neuropathies and myopathies. All must now be excluded in the diagnostic process. New diagnostic criteria, established by arbitration rather than by investigation, may reduce this heterogeneity but they cannot exclude it. Furthermore, patients who fulfil the old criteria but do not satisfy the new ones remain a heterogeneous group. Yet irritable bowel syndrome remains common. Talley and colleagues questioned Minnesota residents about their symptoms; 17% of respondents met the Manning criteria for diagnosis.34 In a similar UK study, 25% of respondents fulfilled the same criteria.35 Strictly speaking, there is no science of the irritable bowel syndrome, for it remains undefined by the methods of science. Like the syndromes of chronic low back pain and headache, the irritable bowel retains its place as a repository of unexplained symptoms.
REFERENCES Irritable bowel syndrome: prevalence, prognosis and Can Med Assoc J 1986; 134: 111-13. 2. Hurst AF. The unhappy colon. Lancet 1935; i: 1483-87. 3. White WH. A study of 60 cases of membranous colitis. Lancet 1905; ii: 1.
Thompson WG. consequences.
1229-35. 4. Bockus HL, Bank J, Wilkinson SA. Neurogenic mucous colitis. Am J Med Sci 1928; 176: 813-29. 5. White BV, Jones CM. Mucous colitis: a delineation of the syndrome with certain observations on its mechanism and on the role of emotional tension as a precipitating factor. Ann Intern Med 1940; 14: 854-72. 6. Ryle JA. Chronic spasmodic affections of the colon and the diseases which they simulate. Lancet 1928; ii: 1115-19. 7. Barker LF. On the management of the spastic colon and mucous colopathy, especially in hypervagotonic persons. Am J Med Sci 1928; 178: 606-15. 8. Jordan SM, Kiefer ED. The irritable colon. JAMA 1929; 93: 592-95. 9. Almy TP. Experimental studies on the irritable colon. Am J Med 1951; 10: 60-67. 10. Chaudhary NA, Truelove SC. The irritable colon syndrome. Q J Med 1962; 31: 307-22. 11. Hislop IG. Psychological significance of the irritable colon syndrome. Gut 1971; 12: 452-57.
1447
12. Esler MD, Goulston KJ. Levels of anxiety in colonic disorders. N Engl J Med 1973; 288: 16-20. 13. Snape WJ, Carlson GJ, Matarazzo SA, Cohen S. Evidence that abnormal myoelectrical activity produces colonic motor dysfunction in the irritable bowel syndrome. Gastroenterology 1977; 72: 383-87. 14. Latimer P, Sarna S, Campbell D, et al. Colonic motor and myoelectrical activity: a comparative study of normal subjects, psychoneurotic patients and patients with irritable bowel syndrome. Gastroenterology
1981; 80: 893-901. Snape WJ, Matarazzo SA, Cohen S. Effect of eating and gastrointestinal hormones on human colonic myoelectrical and motor activity. Gastroenterology 1978; 75: 373-79. 16. Trotman IF, Misiewicz JJ. Sigmoid motility in diverticular disease and the irritable bowel syndrome. Gut 1988; 29: 218-22. 17. Thompson WG. The irritable gut: functional disorders of the alimentary canal. Baltimore: University Park Press, 1979. 18. Manning AP, Thompson WG, Heaton KW, Morns AF. Towards positive diagnosis of the irritable bowel. BMJ 1978; 2: 653-54. 19. Kruis W, Thieme CH, Weinzerl M, et al. A diagnostic score for the irritable bowel syndrome: its value in the exclusion of organic disease. Gastroenterology 1984; 87: 1-7. 20. Whitehead WE, Bosmajian L, Zonderman AB, Costa BJ, Schuster MM. 15.
Symptoms
of
psychologic distress associated with irritable bowel syndrome: comparison of community and medical clinic samples. Gastroenterology 1988; 95: 709-14. 21. Thompson WG, Dotevall G, Drossman DA, Heaton KW. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterol Int 1989; 2: 92-95. 22. Kumar D, Pfeffer J, Wingate DL. Role of psychological factors in the irritable bowel syndrome. Digestion 1990; 45: 80-87. 23. Kellow JE, Langeluddecke PM, Eckersley GM, Jones MP, Tennant CC. Effects of acute psychological stress on small-intestinal motility in health and the irritable bowel syndrome. Scand J Gastroenterol 1992; 27: 53-58.
Talley NJ, Phillips SF, Bruce B, Twomey CK, Zinsmeister AR, Melton LJ. Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome. Gastroenterology 1990; 99: 327-33. 25. Smith RC, Greenbaum DS, Vancouver JB, et al. Psychosocial factors are associated with health care seeking rather than diagnosis in irritable bowel syndrome. Gastroenterology 1990; 98: 293-301. 26. Kumar D, Wingate DL. The irritable bowel syndrome: a paroxysmal motor disorder. Lancet 1985; ii: 973-77. 27. Trotman IF, Price CC. Bloated irritable bowel defined by dynamic 99Tc brain scan. Lancet 1986; ii: 364-66. 28. Kellow JE, Gill RC, Wingate DL. Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome. Gastroenterology 1990; 98: 1208-18. 29. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable bowel syndrome. Gut 1983; 14: 125-32. 30. Kendall GPN, Thompson DG, Day SJ, Lennard-Jones JE. Inter and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. Gut 1990; 31: 1062-68. 31. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distension in irritable bowel syndrome. Gastroenterology 1990; 98: 24.
1187-92. 32. McAllister C, McGrath
F, Fielding JF. Altered skin temperature and electromyographic activity in the irritable bowel syndrome. Biomed
Pharmacother 1990; 44: 399-401. 33. Dinan TG, Barry S, Alchion S, Chua A, Keeling PWN. Assessment of central noradrenergic functioning in irritable bowel syndrome using a neuroendocrine challenge test. J Psychosomatic Res 1990; 34: 575-80. 34. Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991; 101: 927-34. 35. Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ 1992; 304: 87-90.
Clinical approaches to irritable bowel syndrome
Irritable bowel syndrome (IBS) is among the most of gastrointestinal disorders, affecting 15-20% of the population in western countries1 and accounting for 25-50% of referrals to gastroenterologists.2 Its morbidity is responsible for considerable absenteeism from work (second only to the common cold), and repeated visits to physicians lead to patient anxiety, substantial costs to the health-care system, and occasionally to unnecessary abdominal
done during subsequent visits. Therapeutic trials can prove helpful in confirming a provisional diagnosis of IBS, thereby avoiding costly and unnecessary further testing. Confident and clear explanation of the chronic nature of IBS and its implications will help allay patient misconceptions and fears and will provide reassurance during future exacerbations of symptoms.
surgery.33
Symptom criteria A positive diagnosis is critical to successful management
common
Diagnostic strategy After
preliminary diagnosis of IBS has been made, investigations are necessary only to convince both the patient and the physician that other disorders are not being missed. Early performance of a limited number of tests can prevent the erosion of patient confidence and the suspicion of diagnostic uncertainty that may arise if investigations are a
and relies on symptom patterns rather than exhaustive exclusion of other disorders. The criteria of Manning and colleagues-relief of abdominal pain with defaecation, looser or more frequent bowel movements with pain onset, distension, passage of mucus, and sensation of incomplete evacuation4-have been validated and are specific although not highly sensitive.5 An international working panel has further defined the symptom criteria for IBS (table 1).6
History Effective history taking is the key to the diagnosis of IBS. Symptoms typically have a gradual onset in late adolescence or early adulthood and often follow a consistent pattern throughout the patient’s life. Abrupt onset of symptoms late on in life, or a change in a previously characteristic symptom pattern suggests a disorder other than IBS. Upper ADDRESS: Department of Medicine, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA (F. H. Weber, MD, Prof R W. McCallum, MD). Correspondence to Prof R. W. McCallum.
SCIENCE & PRACTICE
Pathophysiology of the irritable bowel syndrome
The irritable bowel syndrome is estimated to affect up to one-quarter of the population of western countries.! Such a common disorder should be well understood, but it is not. I will describe how research into this syndrome has changed, and I shall try to indicate how vague the notion of this condition remains.
Beginnings Mucous colitis Sir William Osler’s The Principles and Practice of Medicine, first published in 1892, contained an entry on mucous colitis, which described "... a tenacious mucus, which may be slimy and gelatinous, like frog-spawn... " passed in strings, strips, or as a continuous tubular cast of the colon. The casts were made of mucus with cell remnants and concretions called intestinal sand; colonic epithelium was normal. Patients were often hysterical, hypochondriacal, depressed, self-centred, neurasthenic, and subject to colicky abdominal pains. Some were constipated, whilst others had nervous diarrhoea. The abdomen, rarely distended, often contained a tender spot in its left upper quadrant. Hurst in 1935 agreed with Osler’s view of mucous colitis,2 describing it as a common disorder before 1914 but exceedingly rare since then. He reported that patients often brought mucus casts to his clinic and passed as much as two ounces of intestinal sand in 24 h. White showed that some cases of mucous colitis were associated with diseases such as carcinoma but like Osler he viewed this condition as a distinct clinical entity.33 Bockus, Bank, and Wilkinson described 50 cases that bore little resemblance to Osler’s mucous colitis.4 Most of their
patients were constipated, dyspeptic, depressed, introspective, exhausted, emotionally unstable, or asthenic; many had a palpable and tender colon. The findings of characteristically clear mucus and shining rectal mucosa seem normal to modem readers. Specific diagnostic criteria were unavailable and patients were identified on the basis of a history of diarrhoea, abdominal pain, and anxiety.5 Spastic colon Colonic spasm was thought to be a common feature of colitis, and was readily detectable by palpation. Ryle described 50 patients with colonic spasm6 who complained mainly of constant lower abdominal pain that became worse with anxiety, smoking, menses, and defaecation; it improved with rest, hot baths, and eating. 30% of patients had constipation, 20% had diarrhoea, and 20% had mucorrhoea. Palpation revealed the colon as a hard and tender cord. He believed that spasm reflected a disorder of autonomic nerve function. Barker identified colonic spasm and mucous colitis as the same entity,7 and speculated that autonomic nerve dysfunction was related to a specific personality disorder. mucous
Irritable colon
Jordan and Kiefer described irritable colon as a colonic musculoneural disturbance present in 30% of outpatients in a gastroenterology practice. They made the diagnosis by barium enema, noting colonic appearance, function, and the distress produced by the enema. Three symptom complexes were common: epigastric distress, nausea, and vomiting; generalised abdominal distress with belching, distension, and anorexia; and left upper quadrant distress with palpitations and heart pain. Colonic neurosis
Early writers on these conditions shared three convictions. First, that the symptoms arise from the colon; second, that the disorder is functional and not morphologically defmable; and third, that the abnormality lies in the nervous system. When they called these colonic disorders neuroses they meant autonomic nervous disorders, which were subdivided into motor, sensory, secretory, and complex. Few commentators presented any data about autonomic and enteric neuronal innervation. In the 1940s, the notion of the irritable bowel syndrome began to replace existing terms. Three essential steps in diagnosis were recommended: to identify symptoms of colonic dysfunction; to exclude organic disease of the colon, and to exclude extracolonic diseases capable of producing colonic symptoms. The principal complaint was usually of aching or cramping lower abdominal pain. Apart from the suspected autonomic disturbance, endocrinopathies and allergies were believed to have important causal roles. Neurosis now came to mean a personality disorder associated with irritable bowel syndrome rather than a primary autonomic disorder. Old science series of experiments completed over 40 years ago, Almy showed that colonic motility changed with acute stress--eg, before and after interviews focusing on emotionally charged subjects, hand immersion in ice-water, and compression of the skull with a metal band equipped with screws.9 Chaudhary and Truelove reported that they could identify predisposing psychological factors in 79% of cases of irritable bowel syndrome, this proportion being the same in patients with painless diarrhoea as in those with spastic colon.10 These factors included marital stress, anxiety over family members, sexual dysfunction, anxiety over career and finances, fear of major illness, and obsessional worrying. Hislop concluded that the syndrome was a physiological In
a
ADDRESS: Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA. Correspondence to Prof J
Christensen,
MD.
1445
concomitant of depressive disorder; 80% of his patients
improved on antidepressant therapy." Esler and Goulston found that patients with diarrhoea-predominant irritable bowel syndrome were significantly more neurotic and anxious than controls."
Interpretation of these data depends on the validity of the personality tests as well as the validity of the diagnosis of bowel disease. Uncertainty about both of these variables led to doubt about the psychosomatic cause of the syndrome. Colonic motor dysfunction
Experiments designed to show colonic motor dysfunction objectively by colonic manometry have been largely unsuccessful. There are few differences between patients with the syndrome and normal controls during manometry of the unstimulated distal colon. 13,14 After colonic stimulation by eating or by balloon distension, patients with irritable bowel syndrome showed a greater response than controls, but the test did not distinguish between diarrhoeapredominant and constipation-predominant forms of the condition.15 Trotman and Misiewicz showed that patients with the syndrome had lower colonic pressures than patients with diverticular disease and healthy controls.16 They emphasised the importance of variables such as the exact location of pressure-sensing devices, bowel preparation, and sedation. A different approach came from the study of electrical slow waves (pacemaking signals) generated in the distal colon.13 There was a disproportionate number of signals at 3/min, the usual frequency being 6/min, in patients with the irritable bowel syndrome compared with controls. The signals were buried in noise and could only be extracted by computer analysis. Although an intense debate followed about the reproducibility of these results, there has been no explanation as to how a slower than normal pacemaker rhythm could account for colon spasm.
Fig 1-Migrating motor complex in the jejunum of a normal human subject. The seven tracings show pressures recorded simultaneously from seven catheters whose open tips lay 3 cm apart. In the fasted state, the pattern varies in a 90-100 min cycle, with a period of quiescence (phase I) of about 70 min, a period of intermittent contractions (phase II) lasting about 10 min, and a period of maximum contractions (phase I 11)of about 5 min. The whole complex migrates slowly caudad. Phase II I constitutes multiple propagated contractions whose velocity exceeds that of the complex (shown by the slanting lines). Abnormal timing of these events is found in ’
diabetic enteroneuropathy, autonomic neuropathies, and the irritable bowel syndrome.
altered bowel habit.9 They found that several symptoms correlated with the failure to find organic disease: the combination of abdominal pain, flatulence, and irregularity of defaecation; symptoms lasting for more than two years; abdominal pain described as "burning, cutting, very strong, or terrible"; alternating constipation and diarrhoea; and pencil-like or pelleted stools, or mucus with stools. Other workers produced slightly different criteria .20 The International Congress of Gastroenterology has proposed a definition that takes account of these different views; it is discussed further in the next article.21 or
New science
Definition
expectation of finding clear-cut psychological and physiological correlates for the irritable bowel syndrome was naive because no concrete and uniformly accepted criteria defined the clinical syndrome. Those who had attempted to provide a definition of the syndrome had written that, although it could not be described precisely, experienced observers knew it when they saw it. The only criterion that was accepted universally was the exclusion of The
organic disease. The view about the need for
accurate
diagnostic criteria was slow to develop. For instance, Thompson collected an assortment of unexplained symptoms together under the label of "the irritable gut", thus creating a single entity out of much that remained unexplained. 17
Manning and colleagues questioned all patients referred investigation of abdominal pain, constipation, or diarrhoea.18 They inquired about 15 symptoms thought to be characteristic of the irritable bowel syndrome, which included pain related to defaecation, non-painful sensations related to defaecation, timing of defaecation, abdominal distension, and mucus discharge. The analysis revealed four symptoms that were significantly correlated to a final diagnosis of irritable bowel syndrome. These symptoms, for
called the Manning criteria, are: looser stools at the onset of pain; more frequent stools at the onset of pain; pain eased after defaecation; and visible abdominal distension. Kruis et al studied patients with abdominal pain, flatulence, now
The formulation of these symptom criteria has stimulated efforts to identify psychological or physiological correlates for the irritable bowel syndrome.
new
Psychological disturbances When patients identified by the Manning criteria are compared with healthy controls and with patients who have benign organic disease of the gut, those with the irritable bowel syndrome score higher in measures of anxiety and obsession, but not in measures of phobia, depression, somatic anxiety, and hysteria.22 Anxiety and obsession are likely to be consequences, not causes, of the symptoms. Kellow et al could not distinguish between patients with the irritable bowel syndrome and normal subjects when observing the effect of acute psychological stress on small intestinal motility. 23 Psychoneurosis as a cause of the syndrome therefore remains to be proven. This conclusion has received support from other investigators.24 However, psychosocial factors may identify health-seeking or illness behaviour.25 Motor dysfunction of the small intestine
psychological stress can alter the pattern of the migrating motor complex (fig 1), a pattern of small intestinal motility which is characteristic of fasting and is partly under the control of the central nervous system 26 In patients with the irritable bowel syndrome, such stress produced a pattern Acute
1446
Fig 2-Jejunal motility
in
a
patient
with partial obstruction of
the ileum. The seven tracings show pressures recorded from seven catheters whose tips lay 3 cm apart. The pattern, both in fed and fasted states, is one of short bursts of intense activity separated by long intervals of rest. These "clustered contractions" are also found in some patients with the irritable bowel syndrome.
of "clustered contractions", which is also found in partial intestinal obstruction (fig 2). Radiographic studies indicating altered small intestinal transit in patients with the syndrome support the notion that small intestinal motility is abnormal. 27 24 h ambulatory monitoring of small intestinal motility in patients with irritable bowel syndrome shows that the duration of the postprandial "fed pattern" of motility is shorter than in normal subjects .28 Cases with diarrhoea-predominant symptoms have abnormally brief intervals between successive migrating motor complexes in the fasted state.
Sensory abnormalities The view that irritable bowel syndrome reflects visceral hyperaesthesia has prompted several studies into the effects on pain perception of rectal distension by balloon inflation.29 Although hypersensitivity is common, the overlap with normal subjects is large. Moreover, some researchers have
been unable to find differences in the rectal pressure volume relation.3° Whitehead and colleagues have suggested altered receptor sensitivity in the rectosigmoid in patients with the irritable bowel syndrome.31
Neurological disorders Higher electromyographic activity and lower digital temperatures are found in patients doing mental arithmetic during baseline measurements and periods of calculation than in controls.32 Dinan et al gave patients and normal subjects a standard dose of desipramine and measured growth hormone release. 11of 13 patients with irritable bowel syndrome showed a blunted response, whilst no patients with peptic ulcer disease and only one normal control showed a similar result. This group concluded that abnormal central alpha-2 receptor function characterises the irritable bowel
syndrome. Comment The irritable bowel syndrome has provided physicians with a diagnostic term that can allude to almost any set of gastrointestinal symptoms that are poorly understood. Speculation and opinion led to explanations of cause in areas of knowledge that were largely unexplored (see table); for
instance, abnormalities of colonic motility when it could not be studied, autonomic and enteric nervous dysfunctions when they were not well understood, and psychoneurosis when there was no way to define it objectively. The need for a more precise definition of this syndrome has led to refinement of the criteria for symptomatic diagnosis. These new criteria focus on defaecatory dysfunction. However, there is still no clear
psychopathology or pathophysiology. The irritable bowel syndrome remains mainly a diagnosis of exclusion. Heterogeneity of pathological processes must exist in such a diagnostic category. Indeed, evidence for such heterogeneity is found if one examines the history of the syndrome. One disease after another has escaped its nosological boundaries: Crohn’s disease, lactase deficiency, lymphocytic colitis, collagenous colitis, and visceral neuropathies and myopathies. All must now be excluded in the diagnostic process. New diagnostic criteria, established by arbitration rather than by investigation, may reduce this heterogeneity but they cannot exclude it. Furthermore, patients who fulfil the old criteria but do not satisfy the new ones remain a heterogeneous group. Yet irritable bowel syndrome remains common. Talley and colleagues questioned Minnesota residents about their symptoms; 17% of respondents met the Manning criteria for diagnosis.34 In a similar UK study, 25% of respondents fulfilled the same criteria.35 Strictly speaking, there is no science of the irritable bowel syndrome, for it remains undefined by the methods of science. Like the syndromes of chronic low back pain and headache, the irritable bowel retains its place as a repository of unexplained symptoms.
REFERENCES Irritable bowel syndrome: prevalence, prognosis and Can Med Assoc J 1986; 134: 111-13. 2. Hurst AF. The unhappy colon. Lancet 1935; i: 1483-87. 3. White WH. A study of 60 cases of membranous colitis. Lancet 1905; ii: 1.
Thompson WG. consequences.
1229-35. 4. Bockus HL, Bank J, Wilkinson SA. Neurogenic mucous colitis. Am J Med Sci 1928; 176: 813-29. 5. White BV, Jones CM. Mucous colitis: a delineation of the syndrome with certain observations on its mechanism and on the role of emotional tension as a precipitating factor. Ann Intern Med 1940; 14: 854-72. 6. Ryle JA. Chronic spasmodic affections of the colon and the diseases which they simulate. Lancet 1928; ii: 1115-19. 7. Barker LF. On the management of the spastic colon and mucous colopathy, especially in hypervagotonic persons. Am J Med Sci 1928; 178: 606-15. 8. Jordan SM, Kiefer ED. The irritable colon. JAMA 1929; 93: 592-95. 9. Almy TP. Experimental studies on the irritable colon. Am J Med 1951; 10: 60-67. 10. Chaudhary NA, Truelove SC. The irritable colon syndrome. Q J Med 1962; 31: 307-22. 11. Hislop IG. Psychological significance of the irritable colon syndrome. Gut 1971; 12: 452-57.
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1981; 80: 893-901. Snape WJ, Matarazzo SA, Cohen S. Effect of eating and gastrointestinal hormones on human colonic myoelectrical and motor activity. Gastroenterology 1978; 75: 373-79. 16. Trotman IF, Misiewicz JJ. Sigmoid motility in diverticular disease and the irritable bowel syndrome. Gut 1988; 29: 218-22. 17. Thompson WG. The irritable gut: functional disorders of the alimentary canal. Baltimore: University Park Press, 1979. 18. Manning AP, Thompson WG, Heaton KW, Morns AF. Towards positive diagnosis of the irritable bowel. BMJ 1978; 2: 653-54. 19. Kruis W, Thieme CH, Weinzerl M, et al. A diagnostic score for the irritable bowel syndrome: its value in the exclusion of organic disease. Gastroenterology 1984; 87: 1-7. 20. Whitehead WE, Bosmajian L, Zonderman AB, Costa BJ, Schuster MM. 15.
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Talley NJ, Phillips SF, Bruce B, Twomey CK, Zinsmeister AR, Melton LJ. Relation among personality and symptoms in nonulcer dyspepsia and the irritable bowel syndrome. Gastroenterology 1990; 99: 327-33. 25. Smith RC, Greenbaum DS, Vancouver JB, et al. Psychosocial factors are associated with health care seeking rather than diagnosis in irritable bowel syndrome. Gastroenterology 1990; 98: 293-301. 26. Kumar D, Wingate DL. The irritable bowel syndrome: a paroxysmal motor disorder. Lancet 1985; ii: 973-77. 27. Trotman IF, Price CC. Bloated irritable bowel defined by dynamic 99Tc brain scan. Lancet 1986; ii: 364-66. 28. Kellow JE, Gill RC, Wingate DL. Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome. Gastroenterology 1990; 98: 1208-18. 29. Ritchie J. Pain from distension of the pelvic colon by inflating a balloon in the irritable bowel syndrome. Gut 1983; 14: 125-32. 30. Kendall GPN, Thompson DG, Day SJ, Lennard-Jones JE. Inter and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. Gut 1990; 31: 1062-68. 31. Whitehead WE, Holtkotter B, Enck P, et al. Tolerance for rectosigmoid distension in irritable bowel syndrome. Gastroenterology 1990; 98: 24.
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F, Fielding JF. Altered skin temperature and electromyographic activity in the irritable bowel syndrome. Biomed
Pharmacother 1990; 44: 399-401. 33. Dinan TG, Barry S, Alchion S, Chua A, Keeling PWN. Assessment of central noradrenergic functioning in irritable bowel syndrome using a neuroendocrine challenge test. J Psychosomatic Res 1990; 34: 575-80. 34. Talley NJ, Zinsmeister AR, Van Dyke C, Melton LJ. Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology 1991; 101: 927-34. 35. Jones R, Lydeard S. Irritable bowel syndrome in the general population. BMJ 1992; 304: 87-90.
Clinical approaches to irritable bowel syndrome
Irritable bowel syndrome (IBS) is among the most of gastrointestinal disorders, affecting 15-20% of the population in western countries1 and accounting for 25-50% of referrals to gastroenterologists.2 Its morbidity is responsible for considerable absenteeism from work (second only to the common cold), and repeated visits to physicians lead to patient anxiety, substantial costs to the health-care system, and occasionally to unnecessary abdominal
done during subsequent visits. Therapeutic trials can prove helpful in confirming a provisional diagnosis of IBS, thereby avoiding costly and unnecessary further testing. Confident and clear explanation of the chronic nature of IBS and its implications will help allay patient misconceptions and fears and will provide reassurance during future exacerbations of symptoms.
surgery.33
Symptom criteria A positive diagnosis is critical to successful management
common
Diagnostic strategy After
preliminary diagnosis of IBS has been made, investigations are necessary only to convince both the patient and the physician that other disorders are not being missed. Early performance of a limited number of tests can prevent the erosion of patient confidence and the suspicion of diagnostic uncertainty that may arise if investigations are a
and relies on symptom patterns rather than exhaustive exclusion of other disorders. The criteria of Manning and colleagues-relief of abdominal pain with defaecation, looser or more frequent bowel movements with pain onset, distension, passage of mucus, and sensation of incomplete evacuation4-have been validated and are specific although not highly sensitive.5 An international working panel has further defined the symptom criteria for IBS (table 1).6
History Effective history taking is the key to the diagnosis of IBS. Symptoms typically have a gradual onset in late adolescence or early adulthood and often follow a consistent pattern throughout the patient’s life. Abrupt onset of symptoms late on in life, or a change in a previously characteristic symptom pattern suggests a disorder other than IBS. Upper ADDRESS: Department of Medicine, University of Virginia, Health Sciences Center, Charlottesville, Virginia 22908, USA (F. H. Weber, MD, Prof R W. McCallum, MD). Correspondence to Prof R. W. McCallum.
