Irritable bowel syndrome

For patient information click here

Overview
In gastroenterology, irritable bowel syndrome (IBS) or spastic colon is a functional bowel disorder characterized by abdominal pain and changes in bowel habits which are not associated with any abnormalities seen on routine clinical testing. It is fairly common and makes up 20–50% of visits to gastroenterologists. Lower abdominal pain, and bloating associated with alteration of bowel habits and abdominal discomfort relieved with defecation are the most frequent symptoms. The abdominal pain type is usually described in a patient as either diarrhea-predominant (IBS-D), constipation-predominant (IBS-C) or IBS with alternating stool pattern (IBS-A). In some individuals, IBS may have an acute onset and develop after an infectious illness characterised by two or more of the following: fever, vomiting, acute diarrhea, or positive stool culture. This post-infective syndrome has consequently been termed "post-infectious IBS" (IBS-PI) and is acute onset Rome II criteria positive. This condition is more homogeneous, being mostly IBS-D and is drawing much clinical investigation.

Chronic functional abdominal pain (CFAP) is quite similar to, but less common than IBS. CFAP can be diagnosed if there is no change in bowel habits.

Because of the name, IBS can be confused with inflammatory bowel disease (IBD).

Symptoms
The symptoms of IBS are abdominal pain in association with frequent diarrhea, constipation, or a change in bowel habits.

Diagnosis
The underlying biochemical cause of IBS is not well established, so there is no specific laboratory test which can be performed to diagnose this condition. Diagnosis of IBS involves excluding conditions which produce with IBS-like symptoms, and then following a procedure to categorize the patient's symptoms.

Because there are many causes of diarrhea and IBS-like symptoms, the American Gastroenterological Association has published a set of guidelines for tests to be performed to diagnose other conditions which may have symptoms similar to IBS. 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 Rome I Criteria, the Rome II Process, 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 criteria, or may use other guidelines based on their own experience and the patient's history. The algorithm may include additional tests to guard against mis-diagnosis of other diseases as IBS. Such "red flag" symptoms may include weight loss, GI bleeding, anemia, or nocturnal symptoms. However, researchers have noted that red flag conditions may not always contribute to accuracy in diagnosis &mdash; for instance, as many as 31% of IBS patients have blood in their stool.

The diagnostic algorithm identifies a name which 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.

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, celiac disease, parasites, food allergies (though considered controversial), and lactose intolerance. See List of causes of diarrhea for other conditions which can cause diarrhea.

Coeliac disease in particular is often misdiagnosed as IBS: Recognizing celiac disease can be difficult because some of its symptoms are similar to those of other diseases. In fact, sometimes celiac disease is confused with irritable bowel syndrome, iron-deficiency anemia caused by menstrual blood loss, Crohn’s disease, diverticulitis, intestinal infections, and chronic fatigue syndrome. As a result, celiac disease is commonly underdiagnosed or misdiagnosed.

Medical conditions that accompany IBS
Researchers have identified several medical conditions, or comorbidities, which appear with greater frequency in patients diagnosed with IBS.


 * Headache, Fibromyalgia, and Depression: A study of 97,593 individuals with IBS identified comorbidities as headache, fibromyalgia, and depression.  Fibromyalgia has also been identified in other studies as a comorbidity of IBS.


 * Inflammatory bowel disease: 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 develop IBD during the study period.  Serum markers associated with inflammation have also been found in patients with IBS (see Causes).


 * Abdominal surgery: A 2005 study published in Digestive Disease Science 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 has reported a statistically significant link between migraine headaches, IBS, and endometriosis.

Etiology
Initially, IBS was considered a psychosomatic illness and the involvement of biological and pathogenic factors was not verified until the 1990s, a process common in the history of emerging infectious diseases. The risk of developing IBS increases six-fold after acute gastrointestinal infection. Post-infection, further risk factors are young age, prolonged fever, anxiety and depression.

Psychosomatic illness
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 somatic, or mental disorder. One paper from the 1980s investigated "learned illness behavior" in patients with IBS and peptic ulcers. Another study suggested that both IBS and stomach ulcer patients would benefit from 15 months of psychotherapy. Later, it would be found that most stomach ulcers were caused by a bacterial infection with Helicobacter pylori.

Additional publications suggesting the role of brain-gut "axis" appeared in the 1990s, such as a study entitled Brain-gut response to stress and cholinergic stimulation in IBS published in the Journal of Clinical Gastrotnerology in 1993. A 1997 study published in Gut magazine suggested that IBS was associated with a "derailing of the brain-gut axis."



Most peptic ulcers are now treated with 1-2 weeks of antibiotic therapy, since it has been discovered that they are caused by a combination of a genetic trait in the patient and infection with the bacteria H. Pylori.

Immune reaction
From the late 1990s, research publications began identifying specific biochemical changes present in tissue biopsies and serum samples from IBS patients that suggested symptoms had an organic rather than psychosomatic cause. These studies identified cytokines and secretory products in tissues taken from IBS patients. The cytokines identified in IBS patients produce inflammation and are associated with the body's immune response.


 * A study showed that intestinal biopsies from patients with constipation predominant IBS secreted higher levels of serotonin in-vitro. Serotonin plays a role in regulating gastrointestinal motility and water content, and can be altered by some diseases and infections.


 * A study of rectal biopsy tissue from IBS patients showed increased levels of cellular structures involved in the production of the cytokine Interleukin 1 Beta.


 * A study of blood samples from IBS patients identified elevated levels of cytokines Tumor necrosis factor-alpha, Interleukin 1, and Interleukin 6 in patients with IBS.


 * A study of intestinal biopsies from IBS patients showed increased levels of protease enzymes used by the body to digest proteins, and by infectious agents to combat the host's immune system.


 * A study of blood samples from IBS patients found elevated levels of antibodies to the protozoan Blastocystis.

Specific forms of immune response that have been implicated in IBS symptoms include Coeliac disease and other Food allergy conditions. Coeliac disease (also spelled "celiac") is an immunoglobulin type A-(IgA) mediated allergic response to the Gliadin protein in gluten grains,which exhibits wide variety of symptoms and can present as IBS. "Some patients with diarrhea-predominant irritable bowel syndrome (IBS-D) may have undiagnosed celiac sprue (CS). Because the symptoms of CS respond to a gluten-free diet, testing for CS in IBS may prevent years of morbidity and attendant expense." "Coeliac disease is a common finding among patients labelled as irritable bowel syndrome. In this sub-group, a gluten free diet may lead to a significant improvement in symptoms. Routine testing for coeliac disease may be indicated in all patients being evaluated for irritable bowel syndrome." Food allergies, particularly those mediated by IgE and IgG-type antibodies have been implicated in IBS.

Active infections


There is research to support IBS being caused by an as-yet undiscovered active infection. Most recently, a study has found that the antibiotic Rifaximin provides sustained relief for 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). 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-celled organism which has been reported to produce symptoms of abdominal pain, constipation and diarrhea in patients, along with headaches and depression, though these reports are contested by some physicians. Studies from research hospitals in various countries 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-celled organism which 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.

Treatment
Treatment for IBS, as for any physiological condition, works best when it successfully addresses the cause of the condition. The various conditions that can cause IBS, outlined in the Diagnosis and  Etiology sections above, require specific treatments. High rates of success in resolving IBS symptoms have been reported when treatment is specifically tailored to the underlying causes revealed through proper testing for the range of known causes of IBS symptoms.

A questionnaire in 2006 designed to identify patients’ perceptions about IBS, their preferences on the type of information they need, as well as educational media and expectations from health care providers, revealed misperceptions about IBS developing into other conditions, including colitis, malnutrition, and cancer.

The survey found IBS patients were most interested in learning about foods to avoid (60%), causes of IBS (55%), medications (58%), coping strategies (56%), and psychological factors related to IBS (55%). The respondents indicated that they wanted their physician to be available via phone or e-mail following a visit (80%), have the ability to listen (80%), and provide hope (73%) and support (63%).

Diet
There are a number of dietary changes a person with IBS can make to prevent the overreaction of the gastrocolic reflex and lessen pain, discomfort, and bowel dysfunction. Having soluble fiber foods and supplements, substituting milk products with soy or rice products, being careful with fresh fruits and vegetables that are high in insoluble fiber, and eating frequent meals of small amounts of food, can all help to lessen the symptoms of IBS. Foods and beverages to be avoided or minimized include red meat, oily or fatty and fried products, milk products (even when there is no lactose intolerance), solid chocolate, coffee (regular and decaffeinated), alcohol, carbonated beverages, especially those containing sorbitol or other artificial sweeteners. Care, however, should be taken to avoid adding foods to the diet to which the patient is allergic or intolerant.

Definitive determination of dietary issues can be accomplished by testing for the physiological effects of specific foods. The ELISA food allergy panel can identify specific foods to which a patient has a reaction. Other testing can determine if there are nutritional deficiencies secondary to diet that may also play a role. Removal of foods causing IgG immune response as measured using the ELISA food panel has been shown to substantially decrease symptoms of IBS in several studies.

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 can lead to abdominal pain, diarrhea, and/or constipation.

Several of the most common dietary triggers are well-established by clinical studies at this point; research has shown that IBS patients are hypersensitive to fats and fructose.

It also appears that some foods are more difficult for the gut as evidenced by elevated food-specific IgG4 antibodies being present, while others increase colonic contractions, which may be painful, due to increased visceral sensitivity in IBS sufferers.

In patients who do not have diarrhea 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. The one meta-analysis that controlled for solubility found that only soluble fiber improved global symptoms of irritable bowel and neither type of fiber reduced pain Positive studies have used 20-30 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 to 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. There is a mistaken presumption that fiber therapy only works for those with constipation. In actuality soluble fiber can act as a counterbalance to both constipation, by retaining water in the bowel, and for diarrhea, by absorbing excess water.
 * Fiber:

Initial treatments
Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opioid or opioid analogs such as loperamide, diphenoxylate or codeine in diarrhea-predominant IBS for mild symptoms.

Laxatives
For patients who do not adequately respond to dietary fiber, osmotic agents such as polyethylene glycol, sorbitol, and lactulose can help avoid 'cathartic colon' which has been associated with stimulant laxatives. Among the osmotic laxatives, 17 to 26 grams/day of polyethylene glycol (PEG) has been well studied.

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 6 patients are treated with antispasmodics, 1 patient will benefit (number needed to treat = 6). Antispasmodics can be divided in two groups: neurotropics and musculotropics. Neurotropics, such as 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. Antispasmodic drugs are also available in combination with tranquilizers or barbiturates, such as chlordiazepoxide and Donnatal. The value of the combination therapies has not been established.

Drugs affecting serotonin (5-HT)
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:

Agonists

 * Tegaserod, a selective 5-HT4 agonist for IBS-C, is available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. On March 30, 2007, the Food and Drug Administration (FDA) requested that Novartis Pharmaceuticals voluntarily discontinue marketing of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events (heart problems) associated with use of the drug. Novartis agreed to voluntarily suspend marketing of the drug in the United States and in many other countries. On July 27, 2007 the Food and Drug Administration (FDA) approved a limited treatment IND program for Zelnorm in the USA to allow restricted access to the medication for patients in need if no comparable alternative drug or therapy is available to treat the disease. The USA FDA had issued two previous warnings about the serious consequences of Tegaserod. In 2005, Tegaserod was rejected as an IBS medication by the European Union. Tegaserod, marketed as Zelnorm in the United States, was the only agent approved to treat the multiple symptoms of IBS (in women only), including constipation, abdominal pain and bloating. A meta-analysis by the Cochrane Collaboration concludes that if 17 patients are treated with typical doses of tegaserod, 1 patient will benefit (number needed to treat = 17).
 * Selective serotonin reuptake inhibitor anti-depressants (SSRIs), because of their serotonergic effect, would seem to help IBS, especially patients who are constipation predominant. Initial crossover studies and randomized controlled trials  support this role.

Antagonists

 * Alosetron, a selective 5-HT3 antagonist for IBS-D, which is only available for women in the United States under a restricted access program, due to severe risks of side-effects if taken mistakenly by IBS-A or IBS-C sufferers.
 * Cilansetron, also a selective 5-HT3 antagonist, is undergoing further clinical studies in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew Cilansetron from the United States regulatory approval process after receiving a "not approvable" action letter from the FDA requesting additional clinical trials.

Other agents
Anti-depressants include both tricyclic antidepressants (TCAs) and the newer selective serotonin reuptake inhibitors (SSRIs). In addition to improving symptoms via treating any co-existing depression, TCAs have anti-cholinergic actions while SSRIs are serotonergic. Thus in theory, TCAs would best treat diarrhea-predominant IBS while SSRIs would best treat constipation-predominant IBS. A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve (number needed to treat = 3). 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.

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.

Enteric coated peppermint oil capsules has been advocated for IBS symptoms in adults and children; however, results from trials have been inconsistent.

For severe diarrhea-predominant IBS, more potent opioids may be used, such as codeine or propoxyphene; refractory cases may even be treated with paregoric, or, more rarely, deodorized tincture of opium or morphine sulfate. The use of opioids remains controversial due to the lack of evidence supporting their benefit and the potential risk of tolerance, physical dependence and addiction.

Cannabis has theoretical support for its role, but has not been subject of clinical studies. Although illegal in many counties, it has been prescribed to patients in nations such as Canada. Some of the argued benefits of cannabis are the reduction of pain and nausea, appetite stimulation, and assisting in falling asleep.

Psychotherapy and hypnotherapy
There is a strong brain-gut component to IBS, and cognitive therapy may improve symptoms in a portion of patients in conjunction with antidepressants. In a randomized controlled trial of referred patients, cognitive behavioral therapy helped even though patients in this study did not have any psychiatric diagnoses.

Gut-directed or gut-specific hypnotherapy or self-hypnosis is one of the most promising areas of IBS treatment. An uncontrolled study shows that symptom reduction/elimination from IBS hypnotherapy can last at least five years.

Relaxation therapy in four 90-minute group sessions was found to help in a randomized controlled trial.

Alternative treatments
Probiotics are generally accepted to be potentially beneficial strains of bacteria and yeast, often found in the human gut. One research study has shown a clear link between the ingestion of Lactobacillus plantarum LP299V and sufferers of IBS who reported resolution of their abdominal pain. Another study showed the utility of B. infantis 35625, a strain of Bifidobacteria, in normalizing bowel movement frequency in sufferers of IBS. Some practitioners of Integrative Medicine now recommend a strain of Lactobacillus known commonly as "LGG" after its discoverers Gorbach and Goldin. This strain in particular has shown an ability to endure the acidic environment of the stomach and survive until presentation to the intestinal tract
 * Probiotics:

A prospective placebo-controlled study found patients with diarrhea predominant IBS taking Saccharomyces boulardii, a probiotic yeast, had a significant reduction on the number and improvement in consistency of bowel movements.

Many sufferers of IBS seek relief using Acupuncture, a component of Traditional Chinese Medicine. The meta-analysis by the Cochrane Collaboration concluded 'Most of the trials included in this review were of poor quality and were heterogeneous in terms of interventions, controls, and outcomes measured. With the exception of one outcome in common between two trials, data were not combined. Therefore, it is still inconclusive whether acupuncture is more effective than sham acupuncture or other interventions for treating IBS'. One practitioner of Traditional Chinese Medicine asserts that IBS has become a bit of a "garbage diagnosis" for some medical practitioners. Traditional Chinese Medicine does not recognize the Western diagnosis of IBS per se, as the named condition has no definitive single test for diagnosis, clear cause, or cure. Traditional Chinese Medicine approaches IBS on an individual symptom-by-symptom basis, rather than recognizing a standard "IBS" diagnosis, which then warrants a blanket "IBS" treatment. According to the National Institutes of Health, "Preclinical studies have documented acupuncture's effects, but they have not been able to fully explain how acupuncture works within the framework of the Western system of medicine that is commonly practiced in the United States."
 * Acupuncture:

Geographics


By Country: Studies have reported that the prevalence of IBS varies by country and by age range examined. The bar graph at right shows the percentage of the population reporting symptoms of IBS in studies from various geographic regions (see table below for references).

The following table contains a list of studies performed in different countries that measured the prevalence of IBS and IBS-like symptoms:

Returning Travelers: A study of United States residents returning from international travel found a high rate of IBS and persistent diarrhea which developed during travel and persisted upon return. The study examined 83 subjects in Utah, most of whom were returning missionaries. Of the 68 who completed the gastrointestinal questionnaire, 27 reported persistent diarrhea that developed while traveling, and 10 reported persistent IBS that developed while traveling.

Economic cost of IBS
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 oganization 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 1990's 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.

Research spending on IBS
The National Institutes of Health provides a searchable database for grant awards since 1974 on its CRISP database, and provides dollar amounts for recent awards on its Intramural Grant Award Page. In 2006, the NIH awarded approximately 56 grants related to IBS, totalling approximately $18,787,710.

Summary
IBS does not lead to more serious conditions in most patients. But it is a source of chronic pain, fatigue and other symptoms, and it increases a patient's medical costs, 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 societal cost.