IRRITABLE BOWEL SYNDROME

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INTRODUCTION

The commonest GI disorder at present is Irritable Bowel Syndrome(IBS). Though first diagnosed 2 centuries ago IBS still remains poorly understood by physicians and patients around the World. With the availability of better technique to study GI motility and visceral functions along with the development of newer concept on importance of brain in regulating gut function significant progress has been made for better understanding of IBS. Here the current knowledge of IBS reviewed.

DEFINITION

            Functional bowel disorder like IBS is defined as chronic , recurrent GI tract disorder without any organic or structural lesion . Various studies have tried to define IBS. Manning criteria (1978), Rome I criteria (1989), Rome II criteria (1998) were few studies to define IBS. The more acceptable definition is Rome II criteria.

Rome II Criteria for diagnosis of IBS

At least 12 weeks, which need not be consecutive in the preceding 12 months of abdominal discomfort or pain that has 2 of the following 3 features

1.      Relieved by defecation

2.      Onset associated with change in stool frequency

3.      Onset associated with changes in stool pain

PREVALENCE AND EPIDEMIOLOGY

            Prevalent Worldwide  affecting 4% to 35% adults, common in woman than man. Woman make up 80% of population with severe IBS. In most patients the symptoms starts in late teenage or early 20s, (3^rd and 4^th decade) and decreases in 6^th and 7^th decades. After 60 years diagnosis of IBS is to be differentiated from other diseases like colon cancer and diverticulitis.

PATHOPHYSIOLOGY

A connection between brain and gut was proposed by Almy and Mullin by observing colonic motility changes related to stressful information. IBS is a complex disorder in which various physiologic process are involved , like abnormalities of intestinal motility, alteration of visceral sensory function , changes in CNS processing of sensory information’s, psychological stress and luminal factors. Interplay between gut and CNS has been called as Brain –Gut axis

1.       Altered gut motility motor activity

In IBS patients antroduodenal manometry study shows discrete clustered contraction of small intestine. These are bursts of rhythmic contractions and associated with abdominal pain. In other very prolonged contractions are seen within colon or small intestine or very high amplitude propagating contractions within the colon, more in postprandial period with episodic abdominal pain. Alteration of migratory motor complex may either delay (constipation ) or accelerate (diarrhoea) intestinal transit . It reflects the exaggeration of normal GI motility pattern. The motility pattern differs in different patients. Colonic myoelectrical & motor activity studies shows abnormalities under stressful conditions in IBS. They may exhibit increased rectosigmoid motor activity upto 3 hours after eating. Provocative  stimuli like inflation of rectal balloon may lead to distention evoked contractile activity. Recording from transverse descending , sigmoid colon show high amplitude of motility index and peak amplitude in diarrhea prone IBS.

2.       Enhanced Visceral Sensitivity:

Abdominal pain is a critical part of the criteria, the cause of which is not yet established. It has been demonstrated that there occurs an increased sensitivity to pain within GI tract (by balloon inflation study at various level in GI tract).Exhibit exaggerated sensory response to visceral stimuli, postprandial pain is related to entry of food to caecum in 74%. The visceral hyperalgesia appears to be selective for mechano-receptor activated stimuli as perception of intestinal mucosal electrical stimulation is normal in IBS.

Lipids lower the threshold for the first sensation of gas, discomfort and pain in IBS. The area of referred pain after lipid ingestion is increased. So postprandial symptoms are explained by a nutrient dependant exaggerated sensory components of gastrocolonic response. IBS patients don’t exhibit increased hypersensitivity anywhere in body. So disturbance is selective to visceral innervations rather than somatic.

The increased response may be due to (a) Increased endorgan sensitivity with recruitment of silent nociceptors. (b) Spinal hyperexcitability with activation nitric oxide and other neurotransmitters.(c) Endogeneous (cortical and brain stem) modulation of caudad nociceptive transmission.Development of long term hyperalgesia due to neuroplasticity resulting in permanent  or semipermanent changes in neural response to chronic or recurrent visceral stimulation.

3.       Influence of CNS

• In patients of IBS sensory processing is altered outside GI tract. It has proved by various studies.
  1. Positron emission tomography scanning of CNS during ballon distention in IBS patients showed increased activity in prefrontal area associated with anxiety , hypervigilence and reduced activity in anterior cingulate cortex an area important for opioid binding. IBS patients exhibit no increased blood flow in the anterior cingulate gyrus but show activation of the prefrontal cortex in response to rectal activation or rectal distention. Activation of frontal lobe may activate a vigilance network and alertness. The anterior cingulate cortex and prefrontal cortex have a reciprocal inhibitory effect. Thus in IBS the preferential activation of prefrontal lobe without activation of anterior cingulate cortex may represent a form of cerebral dysfunction leading to increased visceral pain perception.
  2. Functional MRI also showed different CNS activity in IBS patients.

·         These studies suggest that IBS patients may process sensory information from GI tract differently than non IBS. Besides other, stimuli like stress, anxiety, depression may modulate sensory processing and influence the perception of pain.

4.       Other factors

(a) Infection – Infectious gastroenteritis may increase the like hood of IBS in later life. The mechanism  of post infectious IBS may be due to (i)  Transient or permanent damage of enteric nervous system, the intrinsic nerve supply responsible for coordinating GI peristalsis. (ii) Development of immune hypersensitivity in which repeated exposure to benign substance induces inflammation and altered motility. (iii) Infectious agent initiates a cycle of chronic mucosal inflammation leading to altered gut motility.

Common in women and younger patients. Microbes involved are Campylobacter, Salmonella, Shigella Increased rectal endocrine cells, T – Lymphocytes and gut permeability are acute changes following Campylobacter which contributes to post infective IBS.

(b)Role of physical and sexual abuse

Several studies have shown higher incidence in physical and sexual abuse cases specially in woman. Forms of sexual abuse includes verbal aggression, exhibitionism, sexual harassment, sexual touching, rape. The pathophysiology is unknown and pain threshold is not lowered.

(c) Psychiatric factor

Recorded in 80% cases of IBS.  No single psychiatrics diagnosis associated. Most patient demonstrate exaggerated symptoms . Influences pain threshold, stress alters sensory threshold.

(d) Hormonal

Serotonin (5HT) containing enterochromaffin cells in the colon and postprandial plasma 5HT are increased in Diarrhoea predominant IBS. As 5 HT plays important role in GI motility they are responsible for pathogenesis and treatment by 5 HT antagonist.

DIAGNOSIS

With a through interview and physical examination IBS can be diagnosed at the first visit. Physicians should not down play the symptoms on the ground that they exist in patients mind. Because physiologically and therapeutically definite GI motility and visceral sensation abnormalities exist in IBS patients. The accuracy of diagnosis may be 97% by proper evaluation of symptoms , normal physical examination and normal simple laboratory test. Diagnosis on basis if Rome II criteria in practically less useful for its restrictive nature. Currently American College of Gastroenterology recommends the broad definition for clinicians- Abdominal pain or discomfort associated with altered bowel habit and absence of warning signs or “red flags” suggestive of organic disease.

SYMPTOMS 

The pattern of symptoms (abdominal pain , altered bowel habit) varies from person to person but remain consistent in same individual varying in intensity and frequency. Typically symptoms are intermittent with symptom-free period lasting for days , weeks or months. Rarely patients have daily symptoms.

A. Abdominal pain

Hallmark of IBS. Duration – for at least 12 weeks during preceding 12 months (need not be consecutive) or more than 25% of time during preceding 3 months. Related to defecations anyway . Intensity quality – Varies among patients but remains stable for individual patients. Described as crampy or sharp or burning May be episodic with a background of consistent for individual.  Location:Hypogastium (25%), right side (20%), left side (20%) and epigastrium (10%) . Pain may be mild to be ignored or interfere daily activities. Malnutrition due to inadequate coloric intake is rare. Sleep deprivation is rare as it occurs in day and waking hours. In severe IBS may be associated nocturnal  pain with poor prognosis. Pain often exacerbated by food or stress and relieved by passage of stool or flatus. Females  have worsening of symptoms during premenstrual and menstrual cycle.

B. Bowel habit

Normal bowel movement ranges from 3 per week to 3 per day.  The altered bowel habit varies in patients but remains consistent for individual. Three patterns are observed – Diarrhoea, constipation or alternating diarrhoea and constipation (most common). Patients having diarrhoea usually have normal consistency is morning but subsequent bowel movement becomes loose associated with urgency, abdominal cramp, flatulence and sense of incomplete evacuation. Stools become more liquid associated with mucous and feeling of drained out. Small volumes of loose stool (< 200 ml). Nocturnal diarrhoea does not occur in IBS. Diarrhoea is aggravated by food or stress. May be associated with large amount of mucous. Bleeding is not usually unless associated haemorrhoid and malabsorption and weight loss do not occur. Patients with constipation complains of rocky hard stool (scybala) associated with straining and incomplete evacuation and associated mucous . Initially may be episodic eventually becomes continuous and gradually intractable to laxative treatment.

C. Fecal incontinence

Staining of undergarments occurs in 20% of IBS. More marked in cases of IBS with diarrhoea or diarrhoea alternating with constipation. May be due to repetitive relaxation of sphincter muscles with repetitive colonic spasm.

D.  Bloating and abdominal distention (Gas & Flatulence)

Very common and due to increased abdominal gas or increased sensitivity of gut to normal gas. Some patients of IBS has aerophagia, and  increased belching and flatulence. Though increase in gas is complained intestinal gas amount is normal. IBS has impaired transit and tolerance of intestinal gas and  tendency to reflux gas from distal to proximal.

E. Other constitutional symptoms

1.      Weight loss – No weight loss

(if weight loss question about warning or “Red flag “ sign)

2.      Anaemia /GI bleeding /Stool occult blood – Unusual

3.      Fatigue, myalgia, arthralgia, fever, chill, night sweat – rare

F. Upper GI symptoms

25 to 50% of IBS complain dyspepsia, heart burn, nausea and vomiting. Overlap between IBS and dyspepsiaoccurs . In IBS case 55 % complain dyspepsia and in dysopeptic patients 31.7% have IBS. This functional disorder may fluctuate and indicate a single , extensive G.I disorder. IBS are more prevalent in patients having noncardiac chest pain.

PHYSICAL EXAMINATION

Thorough physical examination is needed to exclude any associated disease or make a second diagnosis. Generally the physical examinations are normal. P/A examination shows some tenderness due to visceral hypersensitivity , rectal spasm and muscular contraction. Any significant mass, tenderness or bleeding warrants other causes. Suggestive features of IBS include recurrence of abdominal pain with altered bowel habit over a period of time without progressive deterioration, onset of symptoms during stress or emotional upset, without any systemic symptoms like fever, weight loss and small volume of stool without evidence of blood. On the other hand the disorder appearing first time in old age , with a progressive course from onset , persistent diarrhoea after 48 hr fast, nocturnal diarrhoea, steatorrhoea excludes IBS.

DIFFERENTIAL DIAGNOSIS

As per the triad of symptoms in IBS the list of D/D is long.

a)            Quality, location , timing of pain may help for specific disease. Pain in epigastric & periumbilical – biliary tract disease, peptic ulcer, intestinal ischaemia, Ca stomach and pancrease.

Postprandial pain with nausea, bloating – gastroparesis, partial intestinal obstruction, giardia and other parasite infestation.

b)            Diarrhoea – Lactase deficiency, lexative abuse, malabsorption, hyperthyroidism , inflammatory bowel disease, infectious diarrhoea.

c)            Constipation – Side effects of drugs like anticholinergics , antihypertensives and antidepressants, hypothyroidism and other endocrinopathies . Acute intermittent porphyria and lead poisoning.

INVESTIGATION

The goal is to: establish early diagnosis, find co-existing and alternative diagnosis, avoid unnecessary procedures. Certain guidelines have been delineated for diagnosis evaluation. They include duration of symptoms , the change in symptoms over time , age and sex, referral status  of the patient, prior diagnosis studies, family history of colorectal malignancy, psychosocial dysfunction. Laboratory features that argues against IBS are – evidence of anaemia, raised ESR, leucocytes or RBC in stool, stool volume > 200 to 300 ml/d.  Although extensive tests were followed in the past but it is now recognized that no test is necessary in younger patients who meet the criteria of IBS and have normal clinical findings without ‘red flag’ signs. But in the era of medical malpractice objective tests are necessary. A complete blood count, measuring ESR and C-reactive protein level is necessary if it is recent . If constipation is predominant estimate thyroid function test . If diarrhoea predominant –stool is tested for leucocytes and subjected to culture and examine for ova or parasites. Stool should be tested  for Clostridium difficile. If persistent  diarrhoea-serological test to exclude Celiac disease because incidence of celiac disease is 10 times more in IBS than normal. Flexible sigmoidoscopy – in young (< 40 years) having altered bowel habit, rectal discomfort. Colonoscopy – In age above 50 years , having family history of inflammatory bowel disease, colorectal cancer or anaemia. Upper GI endoscopy, oesophagogastroduedenoscopyy, ultrasonogram may be done to rule out other causes.

TREATMENT

General Principles : primarily focused on symptomatic relief through various modalities like patient education and reassurance, diet , supportive and behavioral therapy and pharmacotherapy. Successful management requires physicians understanding and patients knowledge and confidence. Chronic nature of the disease requires prolonged cooperative endeavor on the part of physician and patient. Treatment starts at first visit of the patient when the patient develops care and confidence on physician in way of meticulous interview and thorough physical examination. Contributing factors like diet , emotional state professional and interpersonal relationship and fear and concern are to be considered. Patient is to be explained the pathophysiology, influencing factors, chronicity of the disease.

DIET

Though many patients attribute to food allergy, true food allergy is uncommon in IBS. The act of eating may precipitate bloating, gas or abdominal discomfort. Some patients may relate the symptoms to some specific diets which are to be avoided if the symptoms recur on at least 2 occasions of stopping and reintoduction of the diet. The commonest genetic disorder Lactase insufficiency may be associated with IBS. This can be established by inducing symptoms following milk drink or relief of symptoms by giving lactose free diet.

PHARMACOTHERAPY

Due to complex pathophysiology no single agent has been able to cure IBS. Treatment is targeted at relieving individual symptoms. However FDA has approved 2 drugs which relieves multiple symptoms. (a) Tegaserod – Relieves global symptoms  of IBS with constipation (Pain , bloating, discomfort & constipation). (b) Alosetron – Relieves global symptoms of IBS with diarrhoea.

I. CONSTIPATION

1.            For patients of mild symptoms: life style modification, change in diet, use of fibre supplement, daily fluid intake minimum 64 OZ, food with natural fibres, use bathroom at a set time are to be tried.

2.            If this is effective  fiber supplementation like : I) Methylcellulose, psyllium        ii) Polycarbophil, coarse bran iii) Ispaghula husk are used .These products are hydrophilic agents binding water and prevent dehydration . Only three studies have been significant 1 for polycarbophil and 2 for ispaghula husk. These agents produce bloating and distention in 30% cases. Magnesium hydroxide (Tab , Liq) may be used for constipation , though does not relive abdominal pain and bloating. Long term magnesium is harmful in renal insufficiency. Recently fiber supplementation with psyllium has been shown to reduce perception of rectal distention, indicating that fiber may have a positive affect on  visceral afferent function. Beneficial effect of fibers on colonic physiology suggest an effective treatment though results of various trials are variable. Most investigations report increase in stool weight, decrease in colonic transit time , improvement of constipation. A crossover comparison of different fiber preparations found that psyllium produced greater improvement in stool pattern and abdominal pain than bran. Psyllium produces less bloating and distention. Despite equivocal data regarding efficacy stool bulking agents are worth trying in IBS.

3.            Medication includes (a) Lactulose (b) Polyethylene glycol (c) Prostagladin agents – misoprostol (d) Colchicine (e) Tegaserod  (5HT₄ agonist ). 

Tegaserod - Stimulates prokinetic activity by stimulating peristalsis. In constipation tegaserod accelerates intestinal and ascending colon transit. It selectively binds to serotonin type 4 (5 HT₄) receptors in the gut and directly initiates peristalsis. It relieves constipation, accelerates orocaecal transit, bloating and abdominal pain in 2/3^rd patients. It is recommended as Grade A drug for relieving global symptoms. Side effects is diarrhoea and ischaemic colitis.

Table – 1

Selected medications used for constipation in Irritable Bowel Syndrome

II. DIARRHOEA

Peripherally acting opiate based agents are the initial therapy of choice in diarrhoea predominant IBS. Physiologically they produce increase in segmenting colonic contraction, delay in faecal transit, increase in anal pressure and decrease in rectal perception. They are most useful when taken before anticipated stressful events. The use of antidiarrhoeal should be considered as temporary management, with a final aim of gradual withdrawal of drug with substitution of high fiber diet . Medication are  Diphenoxylate HCL – Atropine, Loperamide – By increasing gut transit time it allows more fluid absorption. By increasing external anal sphincter tone decreases incontinence and soiling, Tricyclic antidepressants (TCA) – in low doses decrease frequency , Calcium channel blockers – decrease motility in some cases, Deodorized tincture of opium (DTO), Alosetron – A 5 HT₃ receptor antagonist.

Alosetrin : Evaluated in diarrhoea predominant IBS. Serotonin acting on 5HT₃ receptor enhances the sensitivity of afferent neurons projecting from gut. Alosetron , the drug reduces painful visceral sensation, induces rectal relaxation , increases rectal compliance, delay colonic transit time, improves stool frequency, consistency and urgency. Women respond better  than man. However due to sideeffect like ischaemic colitis the drug has been withdrawn. Newer 5HT₃ receptor antagonist Cilansetron have same effect as alosetron, but needs further follow up trial.

Table – 2

Selected medications used for Diarrhoea in Irritable Bowel Syndrome