Dr.Asgari Assistant professor, Digestive Disease Imamreza hospital, Kermanshah University of Medical Sciences,Kermanshah, Iran. Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habits in the absence of detectable structural abnormalities. No clear diagnostic markers exist for IBS, thus the diagnosis of the disorder is based on clinical presentation.

Throughout the world, about 10–20% of adults and adolescents have symptoms consistent with IBS most studies show a female predominance. often overlap with other functional disorders such as fibromyalgia, headache, backache, and genitourinary symptoms. Severity of symptoms varies and can significantly impair quality of life, resulting in high health care costs.

PATHOPHYSIOLOGY IBS is a gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits in the absence of an identified cause. The pathophysiology of IBS remains uncertain. Although motor abnormalities of the gastrointestinal tract (increased frequency and irregularity of luminal contractions, abnormal transit time) are detectable in some patients with IBS, no predominant pattern of motor activity has emerged as a marker for IBS

Selective hypersensitization of visceral afferent nerves in the gut has been observed in patients with IBS and is one explanation for IBS symptoms. Immunohistologic investigation has revealed mucosal immune system activation characterized by alterations in particular immune cells and markers in some patients with IBS.

The complex ecology of the fecal microflora has led to speculation whether changes in its composition could be associated with IBS. An association between IBS and small intestinal bacterial overgrowth has been conflicting. The role of food in the pathophysiology of IBS is not clear.

familial patterns may also reflect underlying social factors. Associations between specific genes and IBS are under investigation. Psychosocial factors may influence the expression of IBS symptoms

Diagnostic Criteria for Irritable Bowel Syndrome Recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months associated with two or more of the following: 1: Improvement with defecation 2:Onset associated with a change in frequency of stool 3:Onset associated with a change in form (appearance) of stool

C LINICAL F EATURES IBS is a disorder that affects all ages, although most patients have their first symptoms before age 45. Women are diagnosed with IBS two to three times as often as men and make up 80% of the population with severe IBS pain or abdominal discomfort is a key symptom for the diagnosis of IBS. These symptoms should be improved with defecation and/or have their onset associated with a change in frequency or form of stool. Painless diarrhea or constipation does not fulfill the diagnostic criteria to be classified as IBS.

Supportive symptoms that are not part of the diagnostic criteria include defecation straining urgency or a feeling of incomplete bowel movement passing mucus, and bloating

A BDOMINAL P AIN Abdominal pain in IBS is highly variable in intensity and location. frequently episodic and crampy, but it may be superimposed on a background of constant ache. malnutrition due to inadequate caloric intake is exceedingly rare with IBS. Sleep deprivation is also unusual because abdominal pain is almost uniformly present only during waking hours

Pain is often exacerbated by eating or emotional stress and improved by passage of flatus or stools. female patients with IBS commonly report worsening symptoms during the premenstrual and menstrual

A LTERED B OWEL H ABITS Alteration in bowel habits is the most consistent clinical feature in IBS. The most common pattern is constipation alternating with diarrhea, usually with one of these symptoms predominating. At first, constipation may be episodic, but eventually it becomes continuous and increasingly intractable to treatment with laxatives. Stools are usually hard with narrowed caliber

Diarrhea resulting from IBS usually consists of small volumes of loose stools Most patients have stool volumes of <200 mL. Nocturnal diarrhea does not occur in IBS. Diarrhea may be aggravated by emotional stress or eating. Stool may be accompanied by passage of large amounts of mucus. Bleeding is not a feature of IBS unless hemorrhoids are present malabsorption or weight loss does not occur

G AS AND F LATULENCE Patients with IBS frequently complain of abdominal distention and increased belching or flatulence most patients who complain of increased gas generate no more than a normal amount of intestinal gas. Most IBS patients have impaired transit and tolerance of intestinal gas loads. patients with IBS tend to reflux gas from the distal to the more proximal intestine, which may explain the belching.

U PPER G ASTROINTESTINAL S YMPTOMS Between 25 and 50% of patients with IBS complain of dyspepsia heartburn Nausea and vomiting. IBS symptoms are prevalent in noncardiac chest pain patients

IBS may be induced by GI infection. "post infective" IBS occurs more commonly in females and affects younger rather than older patients.

Risk factors for developing post-infectious IBS prolonged duration of initial illness, toxicity of infecting bacterial strain smoking mucosal markers of inflammation, female gender depression Hypochondriasis, and adverse-life events in the preceding 3 months treatment with antibiotics has been associated with increased risk

Approach to the Patient: Irritable Bowel Syndrome diagnosis relies on recognition of positive clinical features and elimination of other organic diseases. A careful history and physical examination are frequently helpful in establishing the diagnosis.

Clinical features suggestive of IBS include: recurrence of lower abdominal pain with altered bowel habits over a period of time without progressive deterioration onset of symptoms during periods of stress or emotional upset absence of other systemic symptoms such as fever and weight loss, and small-volume stool without any evidence of blood.

against the diagnosis of IBS the appearance of the disorder for the first time in old age progressive course from time of onset persistent diarrhea after a 48-h fast presence of nocturnal diarrhea steatorrheal stools

DD Pain due to IBS that occurs in the epigastric or periumbilical area must be differentiated from biliary tract disease, peptic ulcer disorders, intestinal ischemia, and carcinoma of the stomach and pancreas. If pain occurs mainly in the lower abdomen, the possibility of diverticular disease of the colon, inflammatory bowel disease (including ulcerative colitis and Crohn's disease), and carcinoma of the colon must be considered. Postprandial pain accompanied by bloating, nausea, and vomiting suggests gastroparesis or partial intestinal obstruction.

Giardia lamblia or other parasites may cause similar symptoms. When diarrhea is the major complaint(must be ruled out) lactase deficiency laxative abuse malabsorption celiac sprue hyperthyroidism inflammatory bowel disease infectious diarrhea

constipation may be a side effect of many different drugs, such as anticholinergic antihypertensive antidepressant medications. Endocrinopathies such as hypothyroidism hypoparathyroidism

Thus, a younger individual with mild symptoms requires a minimal diagnostic evaluation, while an older person or an individual with rapidly progressive symptoms should undergo a more thorough exclusion of organic disease. Most patients should have a complete blood count and sigmoidoscopic examination stool specimens should be examined for ova and parasites in those who have diarrhea. In patients with persistent diarrhea not responding to simple anti-diarrhea agents, a sigmoid colon biopsy should be performed to rule out microscopic colitis. In those aged >40 years, an air-contrast barium enema or colonoscopy should also be performed

If the main symptoms are diarrhea and increased gas, the possibility of lactase deficiency should be ruled out with a hydrogen breath test or with evaluation after a 3-week lactose-free diet. Some patients with IBS-D may have undiagnosed celiac sprue. In patients with concurrent symptoms of dyspepsia, upper GI radiographs or esophagogastroduodenoscopy may be advisable. In patients with postprandial right upper quadrant pain, an ultrasonogram of the gallbladder should be obtained.

Laboratory features that argue against IBS include 1:anemia 2:elevated sedimentation rate(ESR) 3: presence of leukocytes or blood in stool 4:stool volume >200–300 mL/d

INITIAL THERAPY In patients with mild and intermittent symptoms that do not impair quality of life initially recommend lifestyle and dietary modification alone rather than specific pharmacologic agents In patients with mild to moderate symptoms who fail to respond to initial management and in patients with moderate to severe symptoms that affect quality of life, we suggest pharmacologic therapy as adjunctive treatment

Education and reassurance — It is important to establish a therapeutic clinician-patient relationship to validate the patient's symptoms. Patients should also be counseled that although IBS does not increase their risk of malignancy, it is a chronic disease.

Both a low FODMAP diet and a strict traditional IBS diet (regular meal pattern; avoidance of large meals; reduced intake of fat, insoluble fibers, caffeine, and gas- producing foods such as beans, cabbage, and onions) improve IBS symptoms. Exclusion of gas-producing foods — Patients with IBS should be advised to exclude foods that increase flatulence (eg, beans, onions, celery, carrots, raisins, bananas, apricots, prunes, Brussels sprouts, wheat germ, pretzels, and bagels), alcohol, and caffeine ( به عنوان مثال، لوبیا، پیاز، کرفس، هویج، کشمش، موز، زردآلو، آلو، کلم بروکلی، جوانه گندم، چوب شور، و شیرینی ) ، الکل و کافئین

L ACTOSE AVOIDANCE Patients with known lactose intolerance should be placed on a lactose-restricted diet. We also suggest an empiric trial of a lactose-free diet in patients who complain of persistent abdominal bloating despite exclusion of gas-producing foods.

G LUTEN AVOIDANCE We suggest a two-week trial of a gluten-free diet in patients with diarrhea-predominant IBS (IBS-D) with significant abdominal bloating and flatulence whose symptoms have failed to improve with a low FODMAP diet and avoidance of gas-producing foods. However, there is limited evidence to support gluten avoidance in patients with IBS.

Physical activity should be advised in patients with IBS given a potential benefit with regard to IBS symptoms and the general health benefits of exercise

ADJUNCTIVE PHARMACOLOGIC THERAPY We treat patients with moderate to severe symptoms of irritable bowel syndrome (IBS) that impair quality of life with pharmacologic agents. Since IBS generally presents as a complex of symptoms, treatment should be based on the predominant symptom and subtype. We make incremental changes in therapy at two- to four-week intervals

Reassurance and careful explanation of the functional nature of the disorder Excessive fructose and artificial sweeteners, such as sorbitol or mannitol, may cause diarrhea, bloating, cramping or flatulence.

Stool-Bulking Agents High-fiber diets and bulking agents. Fiber supplementation with psyllium has been shown to reduce perception of rectal distention As some patients may experience increased bloating and gas, we suggest a starting dose of psyllium of one-half to one tablespoon daily. The dose should then be slowly titrated up based on response to treatment. most gastroenterologists consider stool-bulking agents worth trying in patients with IBS-C.

In patients with IBS with constipation (IBS-C) who have failed a trial of soluble fiber (eg, psyllium/ispaghula), we suggest polyethylene glycol (PEG). psyllium We treat patients with persistent constipation despite treatment with PEG with lubiprostone or linaclotidelubiprostone linaclotide Osmotic laxatives — PEG is inexpensive, widely available, and has fewer side effects as compared with other osmotic laxatives (eg, lactulose, milk of magnesia). We initially start with 17 g of powder dissolved in 8 ounces of water once daily and titrate up or down (to a maximum of 34 g daily) to effect. However, side effects of bloating and abdominal discomfort limit the use of PEG. lactulose

Chloride Channel Activators Lubiprostone is a bicyclic fatty acid that stimulates chloride channels in the apical membrane of intestinal epithelial cells. We use lubiprostone in women with IBS with persistent constipation despite PEG. Chloride secretion induces passive movement of sodium and water into the bowel lumen and improves bowel function. Oral lubiprostone was effective in the treatment of patients with constipation-predominant IBS lubiprostone 8 g twice daily for 3 months

Linaclotide is a guanylate cyclase agonist that stimulates intestinal fluid secretion and transit. As the long-term risks of linaclotide are unknown, its role in the treatment of IBS-C is limited to patients with persistent constipation despite treatment with PEGLinaclotide Linaclotide is used for treatment of IBS-C at a dose of 290 micrograms daily. Patients who received linaclotide also demonstrated a significant improvement in secondary endpoints of abdominal pain/discomfort, bloating, straining, stool consistency

In a randomized crossover trial in which 120 patients with IBS-D were assigned to treatment with ondansetron (starting dose 4 mg) or placebo for five weeks, ondansetron significantly improved stool consistency, frequency, and urgency but was not associated with a significant improvement in abdominal painondansetron Abdominal pain and bloating — In patients with abdominal pain due to IBS, we use antispasmodics on an as-needed basis. In patients with IBS with constipation, we initiate antispasmodics only if the abdominal pain persists despite treatment of constipation. In patients with persistent abdominal pain despite antispasmodics, we recommend a trial of antidepressants..

A NTISPASMODIC AGENTS Antispasmodics should be administered on an as-needed basis and/or in anticipation of stressors with known exacerbating effects. Antispasmodics provide short-term relief in symptoms of abdominal pain in patients with IBS, but their long-term efficacy has not been established. Antispasmodic include those that directly affect intestinal smooth muscle relaxation (eg, mebeverine and pinaverine), and those that act via their anticholinergic or antimuscarinic properties (eg, dicyclomine and hyoscyamine)dicyclominehyoscyamine

Antispasmodics anticholinergic drugs may provide temporary relief for symptoms such as painful cramps related to intestinal spasm. anticholinergic drugs inhibit the gastrocolic reflex; hence, postprandial pain is best managed by giving antispasmodics 30 min before meals (Dicyclomine that have less effect on mucous membrane secretions and produce fewer undesirable side effects) Dicyclomine 20 mg orally four times daily as needed Dicyclomine HyoscyamineHyoscyamine to 0.25 mg orally or sublingually three to four times daily as needed Sustained release hyoscyamine to 0.75 mg orally every 12 hourshyoscyamine

Antidiarrheal Agents Peripherally acting opiate-based agents are the initial therapy of choice for IBS-D. When diarrhea is severe, especially in the painless diarrhea variant of IBS, we suggest loperamide 2 mg 45 minutes before a meal on regularly scheduled doses. in patients with alternating diarrhea and constipation (maximum daily dose 16 mg/day).loperamide Eluxadoline is an agent that combines a mu-opioid receptor agonist and a delta-opioid receptor antagonist; it has been approved for treatment of IBS with diarrhea but is not commercially available

Bile acid sequestrants — In patients with persistent diarrhea despite antidiarrheals we use bile acid sequestrants (eg, cholestyramine, colestipol, colesevelam). However, their use is limited by associated gastrointestinal side effects including bloating, flatulence, abdominal discomfort, and constipation.

A NTIDEPRESSANTS Antidepressants have analgesic properties independent of their mood improving effects. Tricyclic antidepressants (TCAs), via their anticholinergic properties, also slow intestinal transit time, which may provide benefit in diarrhea-predominant IBS

For the treatment of abdominal pain in IBS, antidepressants should be started at low doses. The initial dose should be adjusted based upon tolerance and response. Due to the delayed onset of action of antidepressants, three to four weeks of therapy should be attempted before increasing the dose. Amitriptyline, nortriptyline, and imipramine can be started at a dose of 10 to 25 mg at bedtime. Desipramine should be started at a dose of 12.5 to 25 mg at bedtime. If the patient is intolerant of one TCA, another may be tried. For patients with IBS in whom depression is a cofactor, serotonin reuptake inhibitors (SSRIs) can also be used Amitriptylinenortriptylineimipramine Desipramine the selective serotonin reuptake inhibitor (SSRI) paroxetine accelerates orocecal transit, raising the possibility that this drug class may be useful in IBS-C patients. The SSRI citalopram blunts perception of rectal distention

Antiflatulence Therapy The management of excessive gas is seldom satisfactory, except when there is obvious aerophagia or disaccharidase deficiency. Patients should be advised to eat slowly and not chew gum or drink carbonated beverages. Bloating may decrease if an associated gut syndrome such as IBS or constipation is improved. If bloating is accompanied by diarrhea and worsens after ingesting dairy products, fresh fruits, vegetables, or juices, further investigation or a dietary exclusion trial may be worthwhile.

Avoiding flatogenic foods, exercising, losing excess weight, and taking activated charcoal are safe but unproven remedies. Data regarding the use of surfactants such as simethicone are conflicting. Other therapies — Other therapies have been evaluated in patients with IBS (eg, herbs, acupuncture, enzyme supplementation, and mast cell stabilizers [eg:ketotifen]) but their role in the treatment of IBS remains uncertain Pancreatic enzymes reduce bloating, gas, and fullness during and after high-calorie, high- fat meal ingestion.

Modulation of Gut Flora Antibiotic treatment benefits a subset of IBS patients. Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in IBS patients In patients with moderate to severe IBS without constipation, particularly those with bloating, who have failed to respond to other therapies, we suggest a two- week trial of rifaximinrifaximin

Serotonin Receptor Agonist and Antagonists 5-HT3 receptor antagonist such as alosetron reduces perception of painful visceral stimulation in IBS. It also induces rectal relaxation, increases rectal compliance, decreasing colonic motility and secretion. Itis approved for the treatment of severe diarrhea- predominant IBS in female patients whose symptoms have lasted for six months and who have failed to respond to all other conventional treatment

Side effects of ischemic colitis and complications of severe constipation led to the withdrawal of alosetron from the market in the United States. However, following evaluation of postmarketing data, alosetron is now available in the United States but can be prescribed under restricted conditions, at a lower starting dose than previously approved, and by physicians enrolled in the alosetron prescribing program Novel 5-HT4 receptor agonists such as tegaserod exhibit prokinetic activity by stimulating peristalsis. In IBS patients with constipation, tegaserod accelerated intestinal and ascending colon transit.. Diarrhea is the major side effect. However, tegaserod has been withdrawn from the market; a meta-analysis revealed an increase in serious cardiovascular events

Probiotics — Probiotics are not routinely recommended in patients with IBS. Although they have been associated with an improvement in symptoms, the magnitude of benefit and the most effective species and strain are uncertain Bifidobacterium, Lactobacillus infantis showed significant improvement in the composite score for abdominal pain, bloating/distention, and/or bowel movement/nist hzf

A NXIOLYTICS The use of anxiolytic agents in patients with IBS should be limited to short-term (less than two weeks) reduction of acute situational anxiety that may be contributing to symptoms. Side effects of anxiolytics include the risk of habituation, rebound withdrawal, and drug interactions. Furthermore, benzodiazepines may lower pain thresholds by stimulating gamma aminobutyric acid (GABA) receptors, thereby decreasing brain serotonin.

T HANK Y OU

The selective inhibition of gastrointestinal smooth muscle by antispasmodics and peppermint oil reduce stimulated colonic motor activity and may be beneficial in patients with postprandial abdominal pain, gas, bloating, and fecal urgency