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IRRITABLE BOWEL SYNDROME

Irritable bowel syndrome (IBS, or spastic colon) is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements. Diarrhea or constipation may predominate, or they may alternate (classified as IBS-D, IBS-C or IBS-A, respectively). IBS may begin after an infection (post-infectious, IBS-PI), a stressful life event, or onset of maturity without any other medical indicators.
Although there is no cure for IBS, there are treatments that attempt to relieve symptoms, including dietary adjustments, medication and psychological interventions. Patient education and a good doctor-patient relationship are also important.
Several conditions may present as IBS including coeliac disease, fructose malabsorption, mild infections, parasitic infections like giardiasis, several inflammatory bowel diseases, bile acid malabsorption, functional chronic constipation, and chronic functional abdominal pain. In IBS, routine clinical tests yield no abnormalities, although the bowels may be more sensitive to certain stimuli, such as balloon insufflation testing. The exact cause of IBS is unknown. The most common theory is that IBS is a disorder of the interaction between the brain and the gastrointestinal tract, although there may also be abnormalities in the gut flora or the immune system.
IBS does not lead to more serious conditions in most patients. However, it is a source of chronic pain, fatigue, and other symptoms and contributes to work absenteeism. Researchers have reported that the high prevalence of IBS, in conjunction with increased costs, produces a disease with a high social cost. It is also regarded as a chronic illness and can dramatically affect the quality of a sufferer's life.

CLASSIFICATION


IBS can be classified as either diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) or IBS with alternating stool pattern (IBS-A or pain-predominant. In some individuals, IBS may have an acute onset and develop after an infectious illness characterized by two or more of the following: fever, vomiting, diarrhea, or positive stool culture. This post-infective syndrome has consequently been termed "post-infectious IBS" (IBS-PI).

SIGNS AND SYMPTOMS


The primary symptoms of IBS are abdominal pain or discomfort in association with frequent diarrhea or constipation, a change in bowel habits. There may also be urgency for bowel movements, a feeling of incomplete evacuation (tenesmus), bloating or abdominal distention. People with IBS, more commonly than others, have gastroesophageal reflux, symptoms relating to the genitourinary system, chronic fatigue syndrome, fibromyalgia, headache, backache and psychiatric symptoms such as depression and anxiety. Some studies indicate that up to 60% of persons with IBS also have a psychological disorder, typically anxiety or depression.

CAUSES


The cause of IBS is unknown, but several hypotheses have been proposed. The risk of developing IBS increases sixfold after acute gastrointestinal infection. Post-infection, further risk factors are young age, prolonged fever, anxiety, and depression. Publications suggesting the role of brain-gut "axis" appeared in the 1990s, such as the study "Brain-gut response to stress and cholinergic stimulation in IBS" published in the Journal of Clinical Gastroenterology in 1993. A 1997 study published in Gut magazine suggested that IBS was associated with a "derailing of the brain-gut axis." Psychological factors may be important in the etiology of IBS.

ACTIVE INFECTIONS
There is research to support IBS being caused by an as-yet undiscovered active infection. Studies have shown that the nonabsorbed antibiotic rifaximin can provide sustained relief for some IBS patients. While some researchers see this as evidence that IBS is related to an undiscovered agent, others believe IBS patients suffer from overgrowth of intestinal flora and the antibiotics are effective in reducing the overgrowth (known as "small intestinal bacterial overgrowth"). A new study, which has connected cultures of bacteria from the small intestine to a significantly increased occurrence of IBS, may have confirmed this theory. Other researchers have focused on an unrecognized protozoal infection as a cause of IBS as certain protozoal infections occur more frequently in IBS patients. Two of the protozoa investigated have a high prevalence in industrialized countries and infect the bowel, but little is known about them as they are recently emerged pathogens. Blastocystis is a single-cell organism that has been reported to produce symptoms of abdominal pain, constipation and diarrhea in patients though these reports are contested by some physicians. Studies from research hospitals have identified high Blastocystis infection rates in IBS patients, with 38% being reported from London School of Hygiene & Tropical Medicine,47% reported from the Department of Gastroenterology at Aga Khan University in Pakistan and 18.1% reported from the Institute of Diseases and Public Health at University of Ancona in Italy. Reports from all three groups indicate a Blastocystis prevalence of approximately 7% in non-IBS patients. Researchers have noted that clinical diagnostics fail to identify infection, and Blastocystis may not respond to treatment with common antiprotozoals. Dientamoeba fragilis is a single-cell organism that produces abdominal pain and diarrhea. Studies have reported a high incidence of infection in developed countries, and symptoms of patients resolve following antibiotic treatment. One study reported on a large group of patients with IBS-like symptoms who were found to be infected with Dientamoeba fragilis, and experienced resolution of symptoms following treatment. Researchers have noted that methods used clinically may fail to detect some Dientamoeba fragilis infections. It is also found in people without IBS.

DIAGNOSIS


There is no specific laboratory or imaging test that can be performed to diagnose irritable bowel syndrome. Diagnosis of IBS involves excluding conditions that produce IBS-like symptoms, and then following a procedure to categorize the patient's symptoms. Ruling out parasitic infections, lactose intolerance, small intestinal bacterial overgrowth and celiac disease is recommended for all patients before a diagnosis of irritable bowel syndrome is made. In patients over 50 years old it is recommended that they undergo a screening colonoscopy.

DIFFERENTIAL DIAGNOSIS
Colon cancer, inflammatory bowel disease, thyroid disorders and giardiasis can all feature abnormal defecation and abdominal pain. Less common causes of this symptom profile are carcinoid syndrome, microscopic colitis, bacterial overgrowth, and eosinophilic gastroenteritis; IBS is, however, such a common presentation and testing for these conditions would yield such low numbers of positive results that it is considered difficult to justify the expense. Because there are many causes of diarrhea that give IBS-like symptoms, the American Gastroenterological Association published a set of guidelines for tests to be performed to rule out other causes for these symptoms. These include gastrointestinal infections, lactose intolerance, and coeliac disease. Research has suggested that these guidelines are not always followed. Once other causes have been excluded, the diagnosis of IBS is performed using a diagnostic algorithm. Well-known algorithms include the Manning Criteria, the obsolete Rome I and II criteria, the Kruis Criteria, and studies have compared their reliability. The more recent Rome III Process was published in 2006. Physicians may choose to use one of these guidelines, or may simply choose to rely on their own anecdotal experience with past patients. The algorithm may include additional tests to guard against mis-diagnosis of other diseases as IBS. Such "red flag" symptoms may include weight loss, gastrointestinal bleeding, anemia, or nocturnal symptoms. However, researchers have noted that red flag conditions may not always contribute to accuracy in diagnosis - for instance, as many as 31% of IBS patients have blood in their stool many possibly from hemorrhoidal bleeding. The diagnostic algorithm identifies a name that can be applied to the patient's condition based on the combination of the patient's symptoms of diarrhea, abdominal pain, and constipation. For example, the statement "50% of returning travelers had developed functional diarrhea while 25% had developed IBS" would mean that half the travelers had diarrhea while a quarter had diarrhea with abdominal pain. While some researchers believe this categorization system will help physicians understand IBS, others have questioned the value of the system and suggested that all IBS patients have the same underlying disease but with different symptoms.

INVESTIGATIONS
Investigations are performed to exclude other conditions: Stool microscopy and culture (to exclude infectious conditions) Blood tests: Full blood examination, Liver function tests, Erythrocyte sedimentation rate, serological testing for coeliac disease Abdominal ultrasound (to exclude gallstones and other biliary tract diseases) Endoscopy and biopsies (to exclude peptic ulcer disease, coeliac disease, inflammatory bowel disease, malignancies) Hydrogen breath testing (to exclude fructose and lactose malabsorption)

MISDIAGNOSIS
Published research has demonstrated that some poor patient outcomes are due to treatable causes of diarrhea being mis-diagnosed as IBS. Common examples include infectious diseases, coeliac disease, Helicobacter pylori, parasites. Coeliac disease in particular is often misdiagnosed as IBS. The American College of Gastroenterology recommends that all patients with symptoms of IBS be tested for coeliac disease. Bile acid malabsorption is also often missed in patients with diarrhea-predominant IBS. SeHCAT tests suggest that around 30% of D-IBS have this condition and most respond to bile acid sequestrants. Chronic use of certain sedative-hypnotic drugs especially the benzodiazepines may cause irritable bowel like symptoms that can lead to a misdiagnosis of irritable bowel syndrome.

COMORBIDITIES
Researchers have identified several medical conditions, or comorbidities, which appear with greater frequency in patients diagnosed with IBS. Headache, Fibromyalgia, Chronic fatigue syndrome and Depression: A study of 97,593 individuals with IBS identified comorbidities such as headache, fibromyalgia, and depression. A systematic review found that IBS occurs in 51% of chronic fatigue syndrome patients and 49% of fibromyalgia patients, and psychiatric disorders were found to occur in 94% of IBS patients.Inflammatory bowel disease (IBD): Some researchers have suggested that IBS is a type of low-grade inflammatory bowel disease. Researchers have suggested that IBS and IBD are interrelated diseases, noting that patients with IBD experience IBS-like symptoms when their IBD is in remission. A 3-year study found that patients diagnosed with IBS were 16.3 times more likely to be diagnosed with IBD during the study period. Serum markers associated with inflammation have also been found in patients with IBS (see Causes). Abdominal surgery: A recent (2008) study found that IBS patients are at increased risk of having unnecessary cholecystectomy (gall bladder removal surgery) not due to an increased risk of gallstones, but rather to abdominal pain, awareness of having gallstones, and inappropriate surgical indications. A 2005 study reported that IBS patients are 87% more likely to undergo abdominal and pelvic surgery, and three times more likely to undergo gallbladder surgery. A study published in Gastroenterology came to similar conclusions, and also noted IBS patients were twice as likely to undergo hysterectomy. Endometriosis: One study reported a statistically significant link between migraine headaches, IBS, and endometriosis.Other chronic disorders: Interstitial cystitis may be associated with other chronic pain syndromes, such as irritable bowel syndrome and fibromyalgia. The connection between these syndromes is unknown.

MANAGEMENT


A number of treatments have been found to be better than placebo, including fiber, antispasmodics, and peppermint oil.

DIET
Some people with IBS are likely to have food intolerances. In 2007 the evidence base was not strong enough to recommend restrictive diets. Many different dietary modifications have been attempted to improve the symptoms of IBS. Some are effective in certain sub-populations. As lactose intolerance and IBS have such similar symptoms a trial of a lactose-free diet is often recommended.A diet restricting fructose and fructan intake has been shown to successfully treat the symptoms in a dose-dependant manner in patients with fructose malabsorption and IBS. While many IBS patients believe they have some form of dietary intolerance, tests attempting to predict food sensitivity in IBS have been disappointing. One study reported that an IgG antibody test was effective in determining food sensitivity in IBS patients, with patients on the elimination diet experiencing 10% greater symptom reduction than those on a sham diet. More data is necessary before IgG testing can be recommended. There is no evidence that digestion of food or absorption of nutrients is problematic for those with IBS at rates different from those without IBS. However, the very act of eating or drinking can provoke an overreaction of the gastrocolic response in some patients with IBS due to their heightened visceral sensitivity, and this may lead to abdominal pain, diarrhea, and/or constipation. Fiber There is convincing evidence that soluble fiber supplementation (e.g., psyllium) is effective in the general IBS population. It acts as a bulking agent, and for many IBS-D patients, it allows for a more consistent stool. For IBS-C patients, it seems to allow for a softer, moister, more easily passable stool. Insoluble fiber (e.g., bran) has not been found to be effective for IBS. In some people, insoluble fiber supplementation may aggravate symptoms. Fiber might be beneficial in those who have a predominance of constipation. In patients who have constipation predominant irritable bowel, soluble fiber at doses of 20 grams per day can reduce overall symptoms but will not reduce pain. The research supporting dietary fiber contains conflicting, small studies that are complicated by the heterogeneity of types of fiber and doses used. One meta-analysis found that only soluble fiber improved global symptoms of irritable bowel, but neither type of fiber reduced pain. However, an updated meta-analysis by the same authors found that soluble fiber reduced symptoms. Positive studies have used 10-30 grams per day of psyllium seed.One study specifically examined the effect of dose and found that 20 grams of ispaghula husk was better than 10 grams and equivalent to 30 grams per day. An uncontrolled study noted increased symptoms with insoluble fibers. It is unclear if these symptoms are truly increased compared with a control group. If the symptoms are increased, it is unclear if these patients were diarrhea predominant (which can be exacerbated by insoluble fiber, or if the increase is temporary before benefit occurs.

MEDICATION
Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opiate, opioid, or opioid analogs such as loperamide, codeine, diphenoxylate) in diarrhea-predominant IBS for mild symptoms and stronger opiates such as morphine and oxycodone for severe cases. Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms. Serotonin stimulates the gut motility and so agonists can help constipation-predominate irritable bowel, while antagonists can help diarrhea-predominant irritable bowel. Laxatives For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid "cathartic colon" which has been associated with stimulant laxatives. Among the osmotic laxatives, 17-26 grams/day of polyethylene glycol (PEG) has been well studied. Lubiprostone (Amitiza), is a gastrointestinal agent used for the treatment of idiopathic chronic constipation and constipation-predominant IBS. It is well-tolerated in adults, including elderly patients. As of July 20, 2006, Lubiprostone had not been studied in pediatric patients. Lubiprostone is a bicyclic fatty acid (prostaglandin E1 derivative) that acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). Unlike many laxative products, Lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration. Antispasmodics The use of antispasmodic drugs (e.g., anticholinergics such as hyoscyamine or dicyclomine) may help patients, especially those with cramps or diarrhea. A meta-analysis by the Cochrane Collaboration concludes that if seven patients are treated with antispasmodics, one patient will benefit. Antispasmodics can be divided in two groups: neurotropics and musculotropics. Neurotropics, such as a phenobarbital like Donnatal or atropine, act at the nerve fibre of the parasympathicus but also affect other nerves and have side effects. Musculotropics such as mebeverine act directly at the smooth muscle of the gastrointestinal tract, relieving spasm without affecting normal gut motility. Since this action is not mediated by the autonomic nervous system, the usual anticholinergic side effects are absent. Tricyclic antidepressants There is strong evidence that low doses of tricyclic antidepressants can be effective for irritable bowel syndrome. However, there is less robust evidence as to the effectiveness of other antidepressant classes such as SSRIs. Serotonin agonists Tegaserod (Zelnorm), a selective 5-HT4 agonist for IBS-D and cilansetron (also a selective 5-HT3 antagonist) were trialed for irritable bowel syndrome. Due to severe adverse effects, namely ischemic colitis and severe constipation, they are not available or recommended for irritable bowel syndrome. Other agents Magnesium aluminum silicates and alverine citrate drugs can be effective for irritable bowel syndrome. There is conflicting evidence about the benefit of antidepressants in IBS. Some meta-analysis have found a benefit while others have not. A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve. A separate randomized controlled trial found that TCAs are best for patients with diarrhea-predominant IBS. Recent studies have suggested that rifaximin can be used as an effective treatment for abdominal bloating and flatulence, giving more credibility to the potential role of bacterial overgrowth in some patients with IBS. Domperidone, a dopamine receptor blocker and a parasympathomimetic, has been shown to reduce bloating and abdominal pain as a result of an accelerated colon transit time and reduced faecal load, that is a relief from hidden constipation; defecation was similarly improved. The use of opioids is controversial due to the potential risk of tolerance, physical dependence and addiction but can be the only relief for some diarrhea predominant cases when other treatment has been ineffective.

STRESS RELIEF
Reducing stress may reduce the frequency and severity of IBS symptoms. Techniques that may be helpful include: Relaxation techniques such as meditation Physical activities such as yoga or tai chi Regular exercise such as swimming, walking or running.

EXERCISE
Many patients find that exercise helps with IBS. At least 30 minutes of strenuous exercise 5 times a week is recommended.

ALTERNATIVE MEDICINE
Due to often unsatisfactory results from medical treatments for IBS up to 50 percent of people turn to complementary alternative medicine. Probiotics Probiotics can be beneficial in the treatment of IBS, taking 10 billion to 100 billion beneficial bacteria per day is recommended for beneficial results. However, further research is needed on individual strains of beneficial bacteria for more refined recommendations. A number of probiotics have been found to be effective including: Lactobacillus plantarum and Bifidobacteria infantis; however, one review found that only Bifidobacteria infantis showed efficacy. Some yogurt is made using probiotics that may help ease symptoms of irritable bowel syndrome. Herbal remedies Peppermint oil: Enteric coated peppermint oil capsules have been suggested for IBS symptoms in adults and children. There is evidence of a beneficial effect of these capsules and it is recommended that peppermint be trialed in all irritable bowel syndrome patients. Safety during pregnancy has not been established however and caution is required not to chew or break the enteric coating otherwise gastroesophageal reflux may occur as a result of lower esophageal sphincter relaxation. Occasionally nausea and perianal burning occur as side effects. Iberogast: The multi-herbal extract Iberogast was found to be significantly superior to placebo via both an abdominal pain scale and an IBS symptom score after four weeks of treatment. Cannabis Kiwifruit IBS/C Commiphora mukul Plantago ovata There is only limited evidence for the effectiveness of other herbal remedies for irritable bowel syndrome. As with all herbs it is wise to be aware of possible drug interactions and adverse effects. Yoga Yoga may be effective for some with irritable bowel syndrome, especially poses which exercise the lower abdomen. Acupuncture Acupuncture may be worth a trial in select patients, but the evidence base for effectiveness is weak. A meta-analysis by the Cochrane Collaboration found no benefits of acupuncture relative to placebo for IBS symptom severity or IBS-related quality of life.

SEX AND GENDER DIFFERENCES


Women are approximately two to three times more likely to be diagnosed with IBS and four to five times more likely to seek specialty care for IBS than are men.These differences likely reflect a combination of both biological (sex) and social (gender) factors. Studies of female patients with IBS show that symptom severity often fluctuates with the menstrual cycle, suggesting that hormonal differences may play a role. Endorsement of gender-related traits has been associated with quality of life and psychological adjustment in IBS. Greater reductions in quality of life may make women with IBS more likely to seek treatment for their symptoms. More generally, gender differences in healthcare-seeking may also play a role. Gender differences in trait anxiety may contribute to lower pain thresholds in women, putting them at greater risk for a number of chronic pain disorders. Finally, sexual trauma is a major risk factor for IBS, with as many as 33% of all patients reporting such abuse.Because women are at higher risk of sexual abuse than men, gender-related risk of abuse may contribute to the higher prevalence of IBS in women.

HISTORY


One of the first references to the concept of an "irritable bowel" appeared in the Rocky Mountain Medical Journal in 1950. The term was used to categorize patients who developed symptoms of diarrhea, abdominal pain, constipation, but where no well-recognized infective cause could be found. Early theories suggested that the irritable bowel was caused by a psychosomatic or mental disorder.

ECONOMICS


The aggregate cost of irritable bowel syndrome in the United States has been estimated at $1.7-$10 billion in direct medical costs, with an additional $20 billion in indirect costs, for a total of $21.7-$30 billion. A study by a managed care company comparing medical costs of IBS patients to non-IBS controls identified a 49% annual increase in medical costs associated with a diagnosis of IBS. A 2007 study from a managed care organization found that IBS patients incurred average annual direct costs of $5,049 and $406 in out-of-pocket expenses. A study of workers with IBS found that they reported a 34.6% loss in productivity, corresponding to 13.8 hours lost per 40 hour week. A study of employer-related health costs from a Fortune 100 company conducted with data from the 1990s found IBS patients incurred US $4527 in claims costs vs. $3276 for controls. A study on Medicaid costs conducted in 2003 by the University of Georgia's College of Pharmacy and Novartis found IBS was associated in an increase of $962 in Medicaid costs in California, and $2191 in North Carolina. IBS patients had higher costs for physician visits, outpatients visits, and prescription drugs. The study suggested the costs associated with IBS were comparable to those found in asthma patients.

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