ALL ABOUT IRRITABLE BOWEL SYNDROME

Irritable Bowel Syndrome (IBS) is the commonest functional gastrointestinal disorder, and affects about 20% of the world population at some point in their lives. It is a chronic, and sometimes quite a disabling, disorder of the large bowel function. Symptoms include defecation-related abdominal pain, usually associated with diarrhoea or constipation, or both, distension or bloating, and indigestion. The term ‘functional disorder’ is applied to a condition when no structural, biochemical, or haematological derangement is seen associated with the organ that is not functioning normally. With regard to IBS, it essentially means no visible abnormality on inspecting the bowel with the naked eye, or on endoscopy, and no obvious or consistent histological abnormality on microscopic examination.

Epidemiology: IBS is ubiquitous, and spares no single part of the globe, although its prevalence does vary from one region to the other. The frequency of IBS is about the same across races and ethnicities. The condition is more common in women, affecting almost twice as many women, compared to men. Most people with the condition do not see a physician, and seem to accept the symptoms as minor variants of normal life condition. Visit to a doctor is usually prompted by its impact on the daily functionality of the individual in the community and work environment, or by concerns regarding a more serious condition, such as cancer, colitis, or sprue.

The Syndrome: The criteria for diagnosis of the condition have undergone many changes over the years. Even the terminologies for the condition have evolved significantly over several decades. As a medical student and junior resident, this writer knew this condition as a mucous colitis, or a spastic colon, or a nervous or neurogenic colitis. His mother, with no knowledge of modern medicine, knew it as ‘seto aawoon’, which can be translated into English as ‘white dysentery’, quite distinct from actual dysenteric illness presenting with blood and mucus in stool. Sir William Osler, the famed Canadian physician of the 19th century, described patients with ‘mucous colitis’ as hysterical, hypochondriac, neurasthenic, and self-centered, but having normal colonic epithelium. With stringent scientific researches and deliberations by experts in conferences, strict criteria have been laid down and refined in recent times, starting with Rome I to current Rome IV criteria to diagnose the bowel condition as IBS.

Rome IV criteria allows the diagnosis only on the basis of recurrent abdominal pain related to bowel movement, or if associated with alteration in stool frequency or form. Another frequent symptom is bloating. Symptoms must be chronic, with a duration of minimum six months, and with none of the warning signs for organic bowel disease, occurring on average at least once a week over the previous three months.

Criteria

1. Patient has recurrent abdominal pain (≥1 day per week, on average, in the previous 3 months), with an onset ≥6 mo before diagnosis
2. Abdominal pain is associated with at least two of the following three symptoms:

– Pain related to defecation

– Change in frequency of stool

– Change in form (appearance) of stool

3. Patient has none of the following warning signs:

– Age ≥50 yr, no previous colon cancer screening, and presence of symptoms

– Recent change in bowel habit

– Evidence of overt GI bleeding (i.e., melaena or haematochezia)

– Nocturnal pain or passage of stools

– Unintentional weight loss

– Family history of colorectal cancer or inflammatory bowel disease

– Palpable abdominal mass or lymphadenopathy

– Evidence of iron-deficiency anemia on blood testing

– Positive test for stool occult blood

Rome IV criteria has classified IBS into four subtypes, depending upon the stool form and frequency:

1. IBS-D: diarrhea predominant; increased frequency of bowel movement and loose in form
2. IBS-C: constipation predominant; decrease in frequency of bowel movement and stool hard and lumpy
3. IBS-M: mixed form with both diarrhea and constipation
4. IBS- UNSUBTYPED: with no consistent pattern of stool frequency or form.

To rule out organic diseases

IBS IS NOT A DIAGNOSIS OF EXCLUSION. Positive and confident diagnosis of IBS is possible if the criteria mentioned above are adhered to, except perhaps the mentioned age of 50 years, which can be questioned, as we are so often seeing colon cancer among younger people. Biomarkers are being studied, but their accuracy as diagnostic aid remains low.

A complete blood count and a C-Reactive Protein assay and faecal calprotectin can be useful in ruling out inflammatory bowel disease or infective colitis. Coeliac disease should be ruled out by serum assay for t-Tglutaminase in those who fail to respond to IBS management measures. Among IBS-C cases, ruling out obstructive defecation is important, as the latter condition responds well to biofeedback. Paradoxical anal

 

contraction on straining noted at rectal examination is a reliable sign to strongly suspect this condition. Anorectal manometry is needed to confirm the diagnosis. Abdominal bloating, lower abdominal pain, and constipation may also feature in post-menopausal women with ovarian or uterine cancer. Digital rectal and vaginal examination, supplemented by ultrasound scanning, can rule out these conditions.

Pathophysiology: Traditional concept is that of brain initiated gut (brain-gut pathway) disorder due to high association with psychological aberrance, such as anxiety or depression. Inappropriately accentuated response to stress with exaggerated expression of circulating corticotrophin-releasing factor (CRF) is frequently observed among IBS-patients. In about half the cases, it is the other way around. The pathogenesis starts in the gut, and the neuro-psychiatric response manifests later (gut-brain pathway). The neuro-psychiatric reaction exacerbates the primary alterations in the gut. The two pathways are presented here:

 

 

 

 

 

 

 

 

 

 

Bile acid malabsorption with diarrhea may be seen in about 25% of cases diagnosed as IBS-D, especially among those with non-functioning or no gallbladder (cholecystectomy). Terminal ileum can absorb only so much of the secreted bile. The unabsorbed bile enters the large bowel where it acts as a colonic mucosal irritant and stimulates colonic motility and water secretion into the colonic lumen. Special and expensive radio-labeled gamma-emitting isotope based tests (23-seleno-25-homotaurocholic acid or SeHCAT testing) are available in few academic centers in Europe to confirm the diagnosis. What is more practical and easier, however, is a therapeutic trial with a bile acid sequestrant such as cholestyramine or colestipol.

Post-infectious IBS develops in about 20% of patients with acute gastroenteritis caused by bacteria, viruses, or protozoa. In these patients, subtle inflammatory changes can usually be observed on microscopic examination.

Microbiome (the large population of varieties of microbes residing in human bowel, mainly the large intestine) alteration is common among patients with IBS, but no specific pattern has so far been ascertained, except that reduced diversity of microbes in stool samples has been a consistent observation. Two clusters of patients, however, showed abnormal Fermicutes. These patients showed altered bowel transit times. Altered microbiota contributes to abnormal bowel physiology and pain perception through release of many metabolites, including short chain fatty acids, acetic and propionic acids. Altered microbiota also leads to activation of innate immune system with high mucosal expression of toll-like receptor-4 (TLR-4) and release of Beta defensin-2. Dietary modification also alters the microbiome, and this may relieve or aggravate the IBS symptoms. Microbiome pattern may also determine the degree of gas production in the bowel and may be the underlying cause for abdominal distension.

Intestinal gas production and handling: Bloating is an extremely common symptom, with a frequency as high as 96%. It is more common among IBS-C (75%) than in IBS-D patients (41%). More than the increase in gas production, it is the handling of the produced gas that seems to be at fault. Ninety percent of patients with IBS retain gas in the intestine, compared with only 20% of healthy subjects.

Food sensitivity and food intolerance: Data is limited, but adverse reaction to certain foods may induce the onset or exacerbation of IBS in some patients. In cases of food sensitivity, specific immunoglobulin IgG testing in England showed borderline positive tests. It is due to a type III immunological reaction, as opposed to food allergy, which is a type I reaction, induced by IgE antibodies. The latter, for example, peanut allergy, is an immediate reaction associated with angioedema- and urticaria-like eruptions along the bowel mucosa, and manifesting as severe cramps abdominal pain, and vomiting. Occasionally, it may manifest as a full blown anaphylaxis. Intolerance to poorly absorbed starches and fermentable sugars and polyols (FODMAP; fermentable oligo-, di-, mono-saccharides, and polyols) can exacerbate or induce the symptoms of IBS, especially the IBS-D and mixed pattern subtypes. It is a non-immune adverse reaction, and much the more common form of food induced IBS. Lactose intolerance from lactase deficiency also falls in this group, as do congenital sucrase or isomaltase deficiencies. Enzyme deficiency prevents digestion of these sugars in the small bowel. They also increase the luminal osmolality and draw large amount of fluid into the bowel lumen. The unabsorbed sugars enter the large bowel unchanged. In the large bowel, bacteria ferment these sugars and produce large amount of gas and cause bowel dysmotility.

Gluten sensitivity: A subset of IBS-patients may have CD, or in some form, non-celiac gluten sensitivity. American College of Gastroenterology recommends testing for CD in patients with IBS-D, because of increased prevalence of CD in this population. In many celiac-negative patients, however, non-gluten components in wheat may be causing symptoms. A randomized controlled trial of a gluten-free diet in IBS-D, improvement in stool frequency, and gut permeability was shown, especially in HLA DQ2/8–positive subset.

Enhanced intestinal sensory function or intestinal hypersensitivity to minor stimuli, such as mild distension, is also commonly observed in IBS patients. Similarly, alteration in motor function, hypermotility in IBS-D with short transit time, and sluggish motility in IBS-C patients with prolonged transit time, is also common in IBS. Accentuated intestinal sensitivity is an especially more commonly observed phenomenon in women, probably the reason why the condition is more common among women. Enhanced intestinal permeability may be one of the underlying pathogenesis in patients with IBS-D. Immune activation resulting in altered local release of serotonin, which also influences intestinal motor and sensory functions. Contrary to the general understanding that blood chemistry is unaltered in IBS, some patients do show high levels of circulating tumor necrosis factor–alfa, a marker of inflammation, and these patients exhibit high level of anxiety—example of intestinal inflammation directly inducing psychological alteration.

Genetics and early life experience are also important and help to explain family clusters of IBS. Sucrase-isomaltase deficiency among family members may be another cause for family clustering. In a very small subset of cases, mutation in sodium channel gene has been identified. Altered expression by the small bowel mucosa of certain genes responsible for barrier and immune function, ion transport, or mast cell function may underlie the development of IBS.

Treatment of irritable bowel syndrome

Consultation: Consultation, itself, if thoughtfully conducted, can provide a lasting therapeutic benefit. A holistic approach is advised. Positive and emphatic diagnosis, based on patient’s history of symptoms development and absence of warning signs and reassurance about the overall benign outcome of IBS, go a long way in alleviating important symptoms and the resulting anxiety and associated depression. This should accompany unhurried explanation, in simple terms, of the probable pathophysiology underlying patient’s symptoms in each individual case. Patient’s concerns should be diligently listened to, listed in order of the priority attributed to each, and addressed individually. Empathy during consultation has been shown to contribute significantly to symptoms alleviation in a randomized control trial.

Lifestyle: After discussing the diagnosis and prognosis of the condition, the consultation should focus on general lifestyle and daily routine, especially the need for regular exercise and adequate good quality of sleep. Exercise and sleep have both been found to alleviate the symptoms of IBS.

Diet: Diet should be the next consideration, as many patients relate their symptoms to the intake of certain specific foods. Dietary modification is best done under the supervision of an experienced dietitian. Attempt should be made to identify trigger foods, and avoided as much as possible. Small frequent meals, rather than heavy intake, and avoidance of excess of alcohol or caffeine are helpful in reducing the symptoms. Such dietary modification has been shown to be as effective as the diet low in FODMAP, which is much more difficult to adhere to.

Fiber has been a contentious issue in the past, but it is clearer now that insoluble fiber aggravates the symptoms, and soluble fibre such as psyllium husk relieves the symptoms, especially of IBS-C.

Low-FODMAP diet (Fermentable oligo-, di-, mono-saccharides and polyols) are poorly handled and absorbed by the small bowel. Thus, they enter the large bowel unchanged and induce high osmolality in the colonic lumen, drawing large amount of water into the lumen. Colonic bacteria act upon these short-chain carbohydrates and produce excess of gas in the colon. This causes pain, distension, and diarrhoea. Regime of low-FODMAP diet has been shown to be effective in IBS-D, but the quality of evidence is deemed to be low.

Gluten has been pointed out as the offending agent by some IBS patients, despite lack of serologic or histologic evidence. In actual fact, it may not be the gluten, but the fructan or other constituents in wheat that may be responsible for the IBS symptoms.

Useful Medications

1. Antispasmodics are used to relieve pain, but they can worsen the distension. Mebeverine acts especially on the colonic smooth muscle and is a weak antispasmodic. Dicyclomine is slightly more effective and has milder side effects compared to hyoscine. Hyoscine is more effective, but can aggravate constipation and cause dry mouth. Peppermint oil can also has colonic antispasmodic effect through its calcium channel blocking effect and has been shown to significantly reduce symptoms compared to placebo. Pinaverium and otilonium are not available in the country, but drotaverine is sometimes useful in alleviating spasmodic pain.
2. Antibiotics can sometimes relieve the symptoms of IBS, especially the post-infective, non-constipating subset. Non-absorbable antibiotics like Rifaximin are judged most suited for IBS management.
3. Probiotics like Bifidobacterium infantis or Lactobacillus plantarum may be effective in reducing global symptoms and abdominal pain, but it is still unclear which strains of probiotics are the really helpful ones. The quality of evidence to support the use of probiotics remains low.
4. Antidepressants, both tricyclic and the selective serotonin reuptake inhibitors (SSRIs), have been shown to be effective probably due to their role in brain-gut axis and in central pain processing. Tricyclics have anticholinergic properties and slow transit time, and are therefore useful in IBS-D, whereas the SSRIs tend to cause some diarrhea and are therefore useful in IBS-C subtype. Patients should be told that these drugs are being used not for depression but for their neuropathic-pain-modulating effect. Dose should be low in the beginning and built up at regular intervals.
5. Drugs acting on 5-Hydroxytryptamine (5-HT) TYPE-3 receptors: Over expression of 5-HT is an important element in the pathophysiology of IBS. Colonic transit time is slowed down by drugs acting on these receptors. IBS-D is helped by Alosetron. Side effects include constipation, and in rare cases, ischaemic colitis. Ondansetron has been shown to be effective in controlling diarrhea, but not the pain, in patients with IBS-D.
6. Intestinal secretagogues: These drugs, Lubiprostone and Linaclotide, by their action on the enterocytes, increase fluid secretion into the intestinal lumen through secretion of chloride and bicarbonate. They also reduce the transit time. Lubiprostone is a prostaglandin derivative and acts on chloride channel protein-2. Linaclotide is a 14-amino acid peptide and is poorly absorbed. It acts on the Guanylate cyclase C receptor. The drug improves constipation and also reduces abdominal pain. Some patients may experience diarrhea with this drug, but is troublesome in less than 5 percent.
7. Drugs acting on opioid receptors: These drugs slow transit time and reduce pain perception. Loperamide is the classic example. It too worsens abdominal distension. Eluxadoline is the newer one in this group. It too improves diarrhea, but not the abdominal pain. Occasionally, it may cause pancreatitis (0.3%) or spasm of the sphincter of Oddi (0.5%).
8. Histamine receptor antagonists: Histamine and tryptase are released through mucosal mast-cell activation in a subset of patients with visceral hypersensitivity. Ebastine, a H1 receptor blocker, has been shown to induce symptom relief by reducing visceral hypersensitivity.Psychological Therapy Hypnotherapy or cognitive behavioral therapy are seen to be beneficial, but their effects have probably been overestimated. Gut-focused hypnotherapy is found to be as effective as low-FODMAP diet therapy. There is no additional benefit of adding the two, low-FODMAP diet and hypnotherapy. Psychologically trained hypnotherapists are, however, rare in the country.Physical and behavioral therapies Pelvic floor dysfunction is under diagnosed in patients with IBS, especially those with constipation. Paradoxical contraction of the pelvic floor during defecation can cause obstructed defecation. Physiotherapists can retrain patients to relax the pelvic floor through biofeedback. Exercises and biofeedback can also address the problems of incorrect toilet posturing, prolonged time spent in the toilet, and the use of inappropriate methods to trigger the urge to defecation. Even though these are found to be useful tools in the management of IBS, selecting patients for this line of therapy can be a difficult feat for an average practitioner of gastroenterology.IBS Problems Some patients with irritable bowel syndrome can have very severe and intractable symptoms. The tendency in such a patient is to seek an alternative diagnosis. There is erosion of trust in the care provider and worsening of the psychological status, along with physical pain and discomfort. Worsening of pain would prompt the urge to use narcotics. This should be avoided, as the ensuing narcotic bowel syndrome would make the condition even worse. Such patients are best managed by an experienced team comprising a gastroenterologist physician and nurse, psychologist, physiotherapist, and a psychiatrist, providing needed support in all areas of the central problem of IBS.

   Literature reviewed:

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