Irritable bowel syndrome
- 1 Classification
- 2 Symptoms
- 3 Diagnosis
- 4 Pathophysiology
- 5 Treatment
- 6 Epidemiology
- 7 Prognosis
- 8 References
In gastroenterology, irritable bowel syndrome (IBS) or spastic colon is a "a disorder with chronic or recurrent colonic symptoms without a clearcut etiology. This condition is characterized by chronic or recurrent abdominal pain, bloating, mucus in feces, and an erratic disturbance of defecation." IBS 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.
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 diarrhoea, 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 homogenous, being mostly IBS-D and is drawing much clinical investigation.
Because of the name, IBS can be confused with inflammatory bowel disease (IBD), a more serious condition.
The range of symptoms relating to IBS is relatively broad, but the main symptom is usually abdominal pain or discomfort associated with changes in bowel habits in the absence of any apparent structural abnormality. The pain is commonly relieved by defecating or modulated by other triggers of gut motility. Generally there is no pain when patients are asleep. Symptoms usually start in young adulthood.
In the past it was thought that the diagnosis of Irritable Bowel Syndrome relied on a diagnosis of exclusion. That is, if one cannot find a cause then IBS is the diagnosis. Currently the diagnosis of Irritable Bowel Syndrome relies on meeting Rome II inclusion criteria (updated by Rome III criteria) and excluding other illnesses based on history, physical exam, and laboratory testing. Although the Rome II and Rome III criteria were not designed to be a management guideline, it is currently a "gold standard" for the diagnosis of IBS. Unfortunately an IBS diagnosis in an adult patient is still only useful as a tool to rule out more serious problems unless further investigation is employed to discern an addressable condition.
Several sets of diagnostic criteria have been proposed. The importance of meeting diagnostic criteria it to reduce the possibility of underlying pathology. Significant underlying pathology is more common in referral setting than in primary care.
Clinical History alone (Manning Criteria)
In 1978 Manning et al. found , from questionnaire data, that IBS sufferers reported four common symptoms. The Manning Criteria was established to distinguish organic causes for symptoms from those of IBS. The Manning criteria, for the detection of organic gastrointestinal disease, have a sensitivity of 75% and specificity of 60% . The prevalence of organic gastrointestinal disease (other than polyps or diverticulosis) among patients suspected of having irritable bowel is about 20% in a primary care clinic  and about 50% among patients referred to a gastroenterologist . Thus, patients with less than 3 Manning criteria have about a 10% chance of organic gastrointestinal disease in primary care and 40% chance of in referral care. In summary, the clinical history alone, as implemented by the Manning criteria, is not adequate to exclude underling organic illness.
Clinical history and physical examination (Rome Criteria)
In 1992 the Rome I Criteria were established by a multinational committee of specialists, which further refined the Manning Criteria. In 1998 the Rome Working Team proposed changes to the definition and diagnostic criteria for IBS to reflect new research data, and to improve clarity. These criteria have evolved, as the Rome Process has integrated fresh evidence and new conceptual approaches to the condition.
Physicians rely on a variety of procedures and laboratory tests to confirm a diagnosis. The cardinal requirement for the diagnosis of IBS is abdominal pain. The Rome II Criteria is used to diagnose IBS after a careful examination of a sufferer's medical history and physical abdominal examination which looks for any 'red flag' symptoms. More recently, the Rome III criteria, incorporating some changes over the previous set of criteria, have been issued. The Rome II and Rome III efforts have integrated pediatric contents to their set of criteria.
According to the Rome II committees and the Functional Brain Gut Research Group, IBS can be diagnosed based on at least 12 weeks, which need not be consecutive, of the preceding 12 months, there was abdominal discomfort or pain that had two out of three of these features:
- Relieved with defecation; and/or
- Onset associated with a change in frequency of stool; and/or
- Onset associated with a change in form (appearance) of stool.
Symptoms that cumulatively support the diagnosis of IBS:
- Abnormal stool frequency (for research purposes, “abnormal” may be defined as greater than 3 bowel movements per day and less than 3 bowel movements per week);
- Abnormal stool form (lumpy/hard or loose/watery stool);
- Abnormal stool passage (straining, urgency, or feeling of incomplete evacuation);
- Passage of mucus;
- Bloating or feeling of abdominal distention, which is some patients is measurable.
Supportive symptoms of IBS:
- A) Fewer than three bowel movements a week
- B) More than three bowel movements a day
- C) Hard or lumpy stools
- D) Loose (mushy) or watery stools
- E) Straining during a bowel movement
- F) Urgency (having to rush to have a bowel movement)
- G) Feeling of incomplete bowel movement
- H) Passing mucus (white material) during a bowel movement
- I) Abdominal fullness, bloating, or swelling
Diarrhea-predominant: At least 1 of B, D, F and none of A, C, E; or at least 2 of B, D, F and one of A or E. Hard or lumpy stools do not qualify.
Constipation-predominant: At least 1 of A, C, E and none of B, D, F; or at least 2 of A, C, E and one of B, D or F.
Red flag symptoms which are NOT typical of IBS:
- Pain that awakens/interferes with sleep
- Diarrhea that awakens/interferes with sleep
- Blood in the stool (visible or occult)
- Weight loss
- Abnormal physical examination
- The validity and stability of such subtypes over time is unknown and should be the subject of future research.
- Because of the characteristic symptom instability, we prefer the terms IBS with constipation and IBS with diarrhea instead of constipation- and diarrhea-predominant IBS. In this categorical system, many people whose features place them close to a subtype boundary change pattern without a major change in pathophysiology. Moreover, the heterogeneity and variable natural history of IBS significantly limit clinical trials of motility-active drugs and drug therapy in practice.
The sensitivity of the Rome criteria is probably inadequate to exclude organic disease without laboratory testing. The reader must be savvy to whether the sensitivity in a report is for the diagnosis of IBS or for he diagnosis of organic disease. In one study, the Rome criteria was reported to have a sensitivity of 100% and specificity of 65% (when used along with the absence of red flags) for the diagnosis of underlying organic gastrointestinal illness . In this study, diagnostic accuracy for IBS is over 95% when Rome II criteria are met, history and physical exam do not suggest any other cause, and initial laboratory testing is negative . However, this is a single study in a referral population and 91% of the patients already had negative imaging of their colon before the study. In a second study, Rome criteria for organic disease was 71% with a specificity of 85% .
Clinical history, physical examination, and basic laboratory tests (Kruis Criteria)
Irritable bowel is suggested if the score is 44 points or more
The Kruis criteria include an ESR > 10 mm/h, WBC > 10k and Hb < 12 g/dl (females) or <14 g/dl (males). In addition to meeting these positive criteria patients have initial laboratory testing with a complete blood count, basic chemistry panel, and an erythrocyte sedimentation rate . Three studies of the Kruis criteria suggest the sensitivity is about 95% and specificity is 68% for diagnosing organic illness . These values may be adequate to exclude organic disease in primary care, but cannot adequately exclude organic disease in referred patients.
The diagnosis of a functional bowel disorder always presumes the absence of a structural or biochemical explanation for the symptoms. This can be excluded via:
- sigmoidoscopy or colonoscopy
- esophagogastroduodenoscopy (EGD, gastroscopy)
- abdominal ultrasound or CT scan
- blood tests: complete blood count, liver enzymes, electrolytes, renal function, erythrocyte sedimentation rate
- stool chemistry (e.g. tests for exocrine pancreas insufficiency and other malabsorption conditions), stool microbiology, fecal fat
- H2-tests for lactose intolerance and fructose malabsorption. However, the role of lactose is controversial 
- blood tests (immunoglobulin A anti-transglutaminase (tTG) antibodies and, if positive, then IgA antiendomysial antibodies (EMA)) or deep duodenal biopsy for celiac disease.
Initial screening only requires a history and physical exam, as well as a full blood count, electrolytes, renal function, and an erythrocyte sedimentation rate. Additional testing is done when there is a poor response to treatment.
While these modalities may be employed to rule out other causes of abdominal symptoms, they are not necessary to make a diagnosis of IBS. Depending on local practice, many doctors avoid overdiagnosing if the history is clearly suggestive of a functional bowel disorder.
Although few doctors will run a complete set of testing, when it is performed the underlying cause of their symptoms can often be found and treated. Testing for bacterial abnormalities, food allergies (IgG type allergies), and parasites are particularly useful though often not covered by insurance and thus not performed.
Researchers have demonstrated abnormal sensitivity in IBS patients to intestinal and esophageal distention with balloons. However, this approach has not yet become available as a diagnostic test since the diagnostic accuracy is low and clinical utility is not yet high enough. The diagnosis of IBS is made by exclusion as there are no serological (blood) markers. A history of major life stress, anxiety, depression, abuse, or preceding infection may be suggestive, yet not diagnostic. Organs outside the gastrointestinal system may be sources of referred symptoms, and abnormalities should be ruled out. Red flags arguing against an IBS diagnosis include bleeding, weight loss, difficulty swallowing, nocturnal symptoms, incontinence, or onset of symptoms over the age of 50. Screening for ruling out colorectal cancer is still applicable.
IBS is highly prevalent in the Western world, but despite the advancement of many theories, no clear cause has yet been established. IBS may a conglomeration of disorders with similar symptoms but multiple different etiologies (root causes). As with many other medical conditions, there is a lot of speculation about causes, including in the field of alternative medicine. Increasing prevalence in developing countries suggests some possible links to diet and cultural factors.
In studies of twins, some  but not all studies , a genetic role is found. In the two positive studies, IBS concordance in monozygotic twins is 17% - 22% compared to dizygotic twins having IBS concordance of 8% to 9%. In one of the studies further support for genetic influences being a minority contributor, a dizygotic twin with IBS has 15.2% IBS in mothers, compared to 6.7% in their co-twin.
Evidence of visceral hyperalgesia (increased sensitivity to noxious stimuli in the gut) includes perception of pain from distention of a rectal balloon at smaller volumes than in normal patients . However somatic sensitivity testing, such as in controlled pressure on the nails of the hand show that IBS patients have greater pain tolerance than normal patients.
Post-infectious or post-antibiotic
Onset of IBS after an episodes of enteritis  or antibiotics  have been described. A meta-analysis found the prevalence of IBS to 9.8% after enteritis as compared to 1.2% in controls . In these cases, a prolonged immune reaction may be the cause. Patients with IBS after a viral illness may have a self limited course of only 3 to 6 months duration. A second meta-analysis reported "The odds of developing irritable bowel syndrome are increased sixfold after acute gastrointestinal infection. Young age, prolonged fever, anxiety and depression are risk factors for post-infectious irritable bowel syndrome".  The role of premorbid psychological state affecting the outcome of organic illness has been described before.
Food allergies and sensitivities
Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may contribute to symptoms.
Argument continues on the definition of cause as regards IBS and food allergies, but studies demonstrate that IBS symptoms are sometimes caused by immune response to foods and exclusion of those foods to which the immune system is responding results in reduction or elimination of IBS symptoms, a cause and effect link.
More controversial is the connection between bacterial overgrowth and irritable bowel syndrome.  Between 10% and 80% of patients with irritable bowel syndrome have bacterial overgrowth as detected by the lactulose H2 breath test. However, the accuracy of the lactulose H2 breath test is disputed.
Psychological stress—feeling mentally or emotionally tense, troubled, angry, or overwhelmed—may trigger symptoms in people with IBS. One study found that women with IBS have are more likely to report prior physical or sexual abuse; almost half of the patients reported prior abuse .
There are various ways that stress may interact with IBS. First, the colon has a vast supply of nerves that connect it to the brain. These nerves control the normal rhythmic contractions of the colon and cause abdominal discomfort at stressful times. People often experience cramps or "butterflies" when they are nervous or upset. But with IBS, the colon can be overly responsive to even slight conflict or stress. Second, some evidence suggests that IBS is affected by the immune system, which fights infection in the body. The immune system is also affected by stress. Third, the link between stress and IBS may be due to socially stressful situations making the mind more tuned to the sensations that arise in the colon and makes the stressed person perceive these sensations as unpleasant.
There appears to be an overlap of IBS with psychological stress, chronic pelvic pain, fibromyalgia, chronic fatigue syndrome, the American folk medicine use of term hypoglycaemia, and various mental disorders (in a small minority). While no single explanation for this phenomenon exists, it does strengthen the view that there is a neurological and psychological component to IBS. Recent studies indicate that presynaptic neural effects secondary to the release of histamine (part of immune response) is likely related to these problems.
It should be noted that the gut has its own nervous system - the enteric nervous system which has reciprocal connections to the main brain. The discovery of this system has lead to the development of the field of neurogastroenterology.
For all these reasons, stress management is an important part of treatment for IBS. Stress management comprises:
- stress reduction (relaxation) training and relaxation therapies, such as meditation
- counseling and support
- regular exercise such as walking or yoga
- changes to the stressful situations in your life
- adequate sleep
The role of hormones in IBS is not yet fully understood. Menstruation frequently triggers or exacerbates IBS symptoms, while pregnancy and menopause can either worsen or improve symptoms. Hormone replacement therapy is associated with an increased risk of developing IBS.
A survey found 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%).
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 soy or rice products for dairy, being careful with fresh fruits and vegetables that are high in insoluble fiber, and eating regular small amounts, 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, dairy (even when there is no lactose intolerance), solid chocolate, coffee (regular and decaffeinated), alcohol, carbonated beverages (especially those also containing sorbitol), and artificial sweeteners. However, care 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.
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 .
Soluble fiber (psyllium or also called ispaghula husk) is more effective than insoluble fiber (bran). One meta-analysis 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 (also called ispaghula husk) . 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 fiber ), or if the increase is temporary before benefit occurs.
Low FODMAP diet
Medications may consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals (e.g., opioid or opioid analogs such as loperamide (Imodium®), or diphenoxylate (Lomotil®)) in diarrhea-predominant IBS for mild symptoms.
- Anti-diarrheal agents
Regarding laxatives for patients who do not adequately respond to fiber, osmotic agents (polyethylene glycol, sorbitol, and lactulose) are good choices in order to avoid 'cathartic colon' which has been associated with stimulant laxatives . Among the osmotic laxatives, one randomized controlled trial found greater improvement from 2 sachets (26 grams) of polyethylene glycol (PEG) versus or 2 sachets (20 grams) of lactulose . Another randomized controlled trial found no difference between sorbitol and lactulose . A second randomized controlled trial found benefit from a single daily dose of 17 grams. 
Antispasmodics are either muscarinic antagonists or calcium channel blockers (pinaverium, alverine) or serotonin receptor antagonosts (trimebutine) or combined muscarinic and calcium antagonist (propinox). The use of antispasmodic drugs (e.g. anticholinergics such as hyoscine) 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). Antispasmodic drugs are also available in combination with tranquilizers or barbiturates, such as Librax® (chlordiazepoxide and clidinium) and Donnatal® (mixed salts of belladonna alkaloids and phenobarbital), respectively. However, the value of the combination therapies is not clear as the role of tranquilizers is not 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:
- Tegaserod, a selective 5-HT4 agonist for IBS-C, was available for relieving IBS constipation in women and chronic idiopathic constipation in men and women. The USA FDA has issued two warnings about the serious consequences of Tegaserod. In 2005, Tegaserod was rejected as an IBS medication by the European Union; however, it is available in some other countries, but is no longer available in the United States. 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) . In April of 2007, Tegaserod was removed from the U.S. market.
- 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.
- 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.
Rifaximin, a non-absorbable antibiotic, may reduce abdominal bloating and flatulence, especially among patients without constipation predominant irritable bowel, suggesting a role for bacterial overgrowth in some patients with IBS .
Anti-depressents 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). Subsequent randomized controlled trials confirm that TCAs are best for patients with diarrhea-predominant IBS.. SSRIs are discussed above under 'Drugs affecting serotonin'.
Two randomized controlled trials show reduction in gas by subjects taking oral alpha-galactosidase (Beano)  ; however, alpha-galactosidase may interfere with the diabetic medication acarbose .
For severe diarrhea-predominant IBS, more potent opioids may be used, such as codeine or propoxyphene (Darvon®); 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 psychological dependence (addiction).
Cannabis has theoretical support for its role , but has not been subject of clinical studies. Although illegal in the United States, 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 sleep.
Psychotherapy and hypnotherapy
There is a strong brain-gut component to IBS, and cognitive therapy may improve symptoms in a proportion 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. Current research shows that symptom reduction/elimination from IBS hypnotherapy can last at least five years .
Probiotics are generally accepted to be potentially beneficial strains of bacteria and yeast, often found in the human gut. A meta-analysis found benefit from probiotics. The benefit may be srongest in constipation-predominant irritable bowel syndrome. Lactobacillus plantarum (LP299V) has shown inconsistent results in randomized controlled trials with a positive and a negative study. Bifidobacterium animalis DN-173 010 benefited patients in a randomized controlled trial.  Another study showed the utility of B. infantis 35625, a strain of Bifidobacteria in normalizing bowel movement frequency in IBS .
Although not studied in a controlled trial, a strain of Lactobacillus known as "LGG" may be able to endure the acidic environment of the stomach and survive until presentation to the intestinal tract .
Prebiotics are short-chain carbohydrates that may benefit gut microbiota.
Many sufferers of IBS seek relief using Acupuncture, a component of Traditional Chinese Medicine and a discipline representing some of the oldest and most used medical procedures in the world. 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'. Acupuncture continues to find increasingly widespread acceptance in the United States, and it is estimated that nearly 8.7 million Americans have sought its benefits . One practitioner of Tradtional 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 . The concept of Qi is important in Acupuncture, as obstructions to its proper flow throughout the body are considered a contributing factor to illness. Details of the specific mechanisms through which Qi function remain as yet unexplained by Western scientific methods. 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." .
Point prevalence is 10–20% of the general population of Western countries with a much higher lifetime prevalence. Prevalence is similar in India, Japan and China. IBS is less common in Thailand and rural South African areas. In Western countries, but not in India or Sri Lanka, females have a greater risk of developing IBS.
Of the persons who have symptoms of IBS, only a proportion seeks medical help. However, there is not yet a predictor known for who will seek medical help and who will not.
IBS is not fatal nor is it linked to the development of other serious bowel diseases. However, due to the chronic pain, discomfort, and other symptoms, work absenteeism, social phobias, and other negative quality-of-life effects can be common in more serious cases. Individuals who find a caring primary caregiver and/or sufficient self-help options should be able to develop a successful treatment program for their symptoms and lead normal lives.
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