Etiology of IBS
The cause of irritable bowel syndrome (IBS) is unknown. No anatomic cause can be found on laboratory tests, x-rays, and biopsies. Emotional factors, diet, drugs, or hormones may precipitate or aggravate gastrointestinal symptoms. Historically, the disorder was often considered as purely psychosomatic. Although psychosocial factors are involved, IBS is better understood as a combination of physiologic and psychosocial factors.
Physiologic factors
A variety of physiologic factors seem to be involved in IBS symptoms. These factors include
Altered intestinal motility
Increased intestinal sensitivity (visceral hyperalgesia)
Various genetic and environmental factors
Visceral hyperalgesia refers to hypersensitivity to normal amounts of intraluminal distention and heightened perception of pain in the presence of normal quantities of intestinal gas; it may result from remodeling of neural pathways in the brain-gut axis. Some patients (perhaps 1 in 7) have reported their IBS symptoms began after an episode of acute gastroenteritis (termed postinfectious IBS). A subset of patients with IBS has autonomic dysfunctions. However, many patients have no demonstrable physiologic abnormalities, and, even in those who do, the abnormalities may not correlate with symptoms.
Constipation Constipation Constipation is difficult or infrequent passage of stool, hardness of stool, or a feeling of incomplete evacuation. (See also Constipation in Children.) No bodily function is more variable and... read more may be explained by slower colonic transit, and diarrhea Diarrhea Stool is 60 to 90% water. In Western society, stool amount is 100 to 200 g/day in healthy adults and 10 g/kg/day in infants, depending on the amount of unabsorbable dietary material (mainly... read more may be explained by faster colonic transit. Some patients with constipation have fewer colonic high amplitude-propagated contractions, which propel colonic contents over several segments. Conversely, excess sigmoid motor activity may retard transit in functional constipation.
Postprandial abdominal discomfort may be attributed to an exaggerated gastro-colonic reflex (the colonic contractile response to a meal), the presence of colonic high amplitude-propagated contractions, visceral hyperalgesia, or a combination of these factors. Fat ingestion may increase intestinal permeability and exaggerate hypersensitivity. Ingestion of food high in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (collectively called FODMAPs) are poorly absorbed in the small intestine and may increase colonic motility and secretion.
Hormonal fluctuations affect bowel functions in women. Rectal sensitivity is increased during menses but not during other phases of the menstrual cycle. The effects of sex steroids on gastrointestinal transit are subtle. The role of small-bowel bacterial overgrowth in IBS is controversial.
Psychosocial factors
Psychologic distress is common among patients with IBS, especially in those who seek medical care. Some patients have anxiety disorders Overview of Anxiety Disorders Everyone periodically experiences fear and anxiety. Fear is an emotional, physical, and behavioral response to an immediately recognizable external threat (eg, an intruder, a car spinning on... read more , depression Depressive Disorders Depressive disorders are characterized by sadness severe enough or persistent enough to interfere with function and often by decreased interest or pleasure in activities. Exact cause is unknown... read more , or a somatization disorder Overview of Somatization Somatization is the expression of mental phenomena as physical (somatic) symptoms. Disorders characterized by somatization extend in a continuum from those in which symptoms develop unconsciously... read more . Sleep disturbances also coexist. However, stress and emotional conflict do not always coincide with symptom onset and recurrence. Some patients with IBS seem to have a learned aberrant illness behavior (ie, they express emotional conflict as a gastrointestinal complaint, usually abdominal pain). The physician evaluating patients with IBS, particularly those with refractory symptoms, should investigate for unresolved psychologic issues, including the possibility of sexual or physical abuse. Psychosocial factors also affect the outcome in IBS.
Symptoms and Signs of IBS
Irritable bowel syndrome tends to begin in adolescence and the 20s, causing bouts of symptoms that recur at irregular periods. Onset in late adult life is less common. Symptoms of IBS rarely rouse the sleeping patient. Symptoms are often triggered by food or by stress.
Patients have abdominal discomfort, which varies considerably but is often located in the lower abdomen, is steady or cramping in nature, and is related to defecation. In addition, abdominal discomfort is temporally associated with alterations in stool frequency (increased in diarrhea-predominant IBS and decreased in constipation-predominant IBS) and consistency (ie, loose or lumpy and hard). Pain or discomfort related to defecation is likely to be of bowel origin; that associated with exercise, movement, urination, or menstruation usually has a different cause.
Although bowel patterns are relatively consistent in most patients, it is not unusual for patients to alternate between constipation and diarrhea. Patients may also have symptoms of abnormal stool passage (straining, urgency, or feeling of incomplete evacuation), pass mucus, or complain of bloating or abdominal distention. Many patients also have symptoms of dyspepsia. Extraintestinal symptoms (eg, fatigue, fibromyalgia, sleep disturbances, chronic headaches) are common.
Diagnosis of IBS
Clinical evaluation, based on Rome criteria
Screening for organic causes with basic laboratory tests and sigmoidoscopy or colonoscopy
Other tests for patients with red flag findings (eg, rectal blood, weight loss, fever)
Diagnosis of irritable bowel syndrome is based on characteristic bowel patterns, time and character of pain, and exclusion of other disease processes through physical examination and routine diagnostic tests.
Red flags
Diagnostic testing should be more intensive when the following red flags are present either at initial presentation or at any time after diagnosis:
Older age
Fever
Weight loss
Rectal bleeding
Vomiting
Differential diagnosis
Because patients with IBS can develop organic conditions, testing for other conditions should also be considered in patients who develop alarm symptoms or markedly different symptoms during the course of IBS. Common illnesses that may be confused with IBS include
Laxative abuse
Microscopic colitis
Bile acid diarrhea
However, uninflamed colonic diverticula do not cause symptoms, and their presence should not be considered explanatory.
The bimodal age distribution of patients with inflammatory bowel disease makes it imperative to evaluate both younger and older patients. In patients > 60 with acute symptoms, ischemic colitis Ischemic Colitis Ischemic colitis is a transient reduction in blood flow to the colon. Diagnosis is by CT or colonoscopy. Treatment is supportive with IV fluids, bowel rest, and antibiotics. Necrosis may occur... read more 
should be considered. Patients with constipation and no anatomic lesion should be evaluated for hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones... read more 
and hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism, vitamin... read more . If the patient’s symptoms suggest malabsorption Overview of Malabsorption Malabsorption is inadequate assimilation of dietary substances due to defects in digestion, absorption, or transport. Malabsorption can affect macronutrients (eg, proteins, carbohydrates, fats)... read more , tropical sprue Tropical Sprue Tropical sprue is a rare acquired disease, probably of infectious etiology, characterized by malabsorption and megaloblastic anemia. Diagnosis is clinical and by small-bowel biopsy. Treatment... read more , celiac disease Celiac Disease Celiac disease is an immunologically mediated disease in genetically susceptible people caused by intolerance to gluten, resulting in mucosal inflammation and villous atrophy, which causes malabsorption... read more 
, and Whipple disease Whipple Disease Whipple disease is a rare systemic illness caused by the bacterium Tropheryma whipplei. Main symptoms are arthritis, weight loss, abdominal pain, and diarrhea. Diagnosis is by small-bowel biopsy... read more must be considered. Defecatory disorders should be considered as a cause of constipation in patients who report symptoms of difficult defecation.
Rare causes of diarrhea include hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms are many and include tachycardia, fatigue, weight loss, nervousness, and tremor... read more 
, medullary cancer of the thyroid Medullary Thyroid Carcinoma There are 4 general types of thyroid cancer. Most thyroid cancers manifest as asymptomatic nodules. Rarely, lymph node, lung, or bone metastases cause the presenting symptoms of small thyroid... read more or carcinoid syndrome Carcinoid Syndrome Carcinoid syndrome develops in some people with carcinoid tumors and is characterized by cutaneous flushing, abdominal cramps, and diarrhea. Right-sided valvular heart disease may develop after... read more 
, gastrinoma Gastrinoma A gastrinoma is a gastrin-producing tumor usually located in the pancreas or the duodenal wall. Gastric acid hypersecretion and aggressive, refractory peptic ulceration result (Zollinger-Ellison... read more , and vipoma Vipoma A vipoma is a non-beta pancreatic islet cell tumor secreting vasoactive intestinal peptide (VIP), resulting in a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). Diagnosis... read more . However, these causes of diarrhea are typically accompanied by stool volumes > 1000 mL daily, which differentiates them from IBS.
History
Particular attention should be given to the character of the pain, bowel habits, familial interrelationships, and drug and dietary histories. Equally important are the patient’s overall emotional state, interpretation of personal problems, and quality of life. The quality of the patient–physician interaction is key to diagnostic and therapeutic efficacy.
The Rome criteria are standardized symptom-based criteria for diagnosing IBS. The Rome criteria require the presence of abdominal pain for at least 1 day/week in the last 3 months along with ≥ 2 of the following (1 Diagnosis reference Irritable bowel syndrome is characterized by recurrent abdominal discomfort or pain with at least two of the following characteristics: relation to defecation, association with a change in frequency... read more ):
Pain that is related to defecation.
Pain is associated with a change in frequency of defecation.
Pain is associated with a change in consistency of stool.
Physical examination
Patients generally appear to be healthy. Palpation of the abdomen may reveal tenderness, particularly in the left lower quadrant, at times associated with a palpable, tender sigmoid. A digital rectal examination, including a test for occult blood, should be done on all patients. In women, a pelvic examination helps rule out ovarian tumors and cysts or endometriosis, which may mimic IBS.
Testing
(See also the American Gastroenterological Association's guidelines on the laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults [IBS-D].)
The diagnosis of IBS can reasonably be made using the Rome criteria as long as patients have no red flag findings, such as rectal bleeding, weight loss, and fever, or other findings that might suggest another etiology. Many patients with IBS are overtested; however, complete blood count, biochemical profile (including liver tests), serologic markers for celiac disease (tissue-transglutaminase IgA with an IgA level), stool examination for infection (in patients with diarrhea predominance), thyroid-stimulating hormone and calcium for patients with constipation, and flexible sigmoidoscopy or colonoscopy should be considered. In patients presenting with chronic diarrhea, fecal calprotectin or fecal lactoferrin should be the first-line tests to screen for inflammatory bowel disease. Chronic diarrhea should also prompt testing for Giardia Diagnosis Giardiasis is infection with the flagellated protozoan Giardia duodenalis (G. lamblia, G. intestinalis). Infection can be asymptomatic or cause symptoms ranging from intermittent flatulence... read more . An antigen test or a polymerase chain reaction test for Giardia is recommended.
During flexible fiberoptic proctosigmoidoscopy, introduction of the instrument and air insufflation frequently trigger bowel spasm and pain. The mucosal and vascular patterns in IBS usually appear normal. Colonoscopy is preferred for patients > 50 to exclude colonic polyps and tumors. In patients with chronic diarrhea, particularly older women, mucosal biopsy can rule out possible microscopic colitis.
Additional studies (such as ultrasonography, CT, barium enema x-ray, upper gastrointestinal esophagogastroduodenoscopy, and small-bowel x-rays) should be undertaken only when there are other objective abnormalities. Fecal fat excretion or pancreatic elastase should be measured when there is a concern about steatorrhea. Small-bowel evaluation (eg, enteroscopy, capsule endoscopy) is recommended when malabsorption is suspected. Testing for carbohydrate intolerance or small-bowel bacterial overgrowth should be considered in appropriate circumstances.
Intercurrent disease
Patients with IBS may subsequently develop additional gastrointestinal disorders, and the clinician must not summarily dismiss their complaints. Changes in symptoms (eg, in the location, type, or intensity of pain; in bowel habits; in constipation and diarrhea) and new symptoms or complaints (eg, nocturnal diarrhea) may signal another disease process. Other symptoms that require investigation include fresh blood in the stool, weight loss, very severe abdominal pain or unusual abdominal distention, steatorrhea or noticeably foul-smelling stools, fever or chills, persistent vomiting, hematemesis, symptoms that wake the patient from sleep (eg, pain, the urge to defecate), and a steady progressive worsening of symptoms. Patients > 40 are more likely than younger patients to develop an intercurrent physiologic illness.
Diagnosis reference
1. Lacy BE, Mearin F, Chang L, et al: Bowel disorders. Gastroenterology 150:1393–1407, 2016. doi: 10.1053/j.gastro.2016.02.031
Treatment of IBS
Support and understanding
Normal diet, avoiding gas-producing and diarrhea-producing foods
Increased fiber intake and hydration for constipation
Drug therapy directed at the dominant symptoms
Therapy is directed at specific symptoms. An effective therapeutic relationship is essential for effectively managing IBS. Patients should be invited to express not only their symptoms but also their understanding of their symptoms and the reasons prompting a visit to the health care practitioner (eg, fear of serious disease). Patients should be educated about the disorder (eg, normal bowel physiology and the bowel’s hypersensitivity to stress and food) and reassured, after appropriate tests, about the absence of a serious or life-threatening disease. Appropriate therapeutic goals (eg, expectations regarding the normal course or variability in symptoms, adverse effects of drugs, the appropriate and available working relationship between the physician and the patient) should be established.
Finally, patients can benefit by being actively involved in the management of their condition. When successful, this can enhance the patient’s motivation to adhere to treatment, foster a more positive physician–patient relationship, and mobilize the coping resources of even the most chronically passive patients. Psychologic stress, anxiety, or mood disorders should be identified, evaluated, and treated. Regular physical activity helps relieve stress and assists in bowel function, particularly in patients with constipation.
(See also the American College of Gastroenterology's monograph on management of irritable bowel syndrome.)
Diet
In general, a normal diet can be followed. Meals should not be overly large, and eating should be slow and paced. Patients with abdominal distention and increased flatulence may benefit from reducing or eliminating beans, cabbage, and other foods containing fermentable carbohydrates. Reduced intake of sweeteners (eg, sorbitol, mannitol, fructose), which are constituents of natural and processed foods (eg, apple and grape juice, bananas, nuts, raisins), may alleviate flatulence, bloating, and diarrhea. Patients with evidence of lactose intolerance should reduce their intake of milk and dairy products. Patients can try reducing their intake of the aforementioned food categories one at a time and noting the effect on their symptoms, or they can try a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet, which restricts all of the aforementioned food categories. In addition, a low-fat diet may reduce postprandial abdominal symptoms.
Patients should be encouraged to drink more fluids. Dietary fiber supplements may soften stool and improve the ease of evacuation. Psyllium hydrophilic mucilloid with two glasses of water may be used. However, excessive use of fiber can lead to bloating and diarrhea, so fiber doses must be individualized. Occasionally, flatulence may be reduced by switching to a synthetic fiber preparation (eg, methylcellulose).
Drug therapy
(See also the American Gastroenterological Association’s technical review and guideline on pharmacologic management of irritable bowel syndrome.)
Drug therapy is directed toward the dominant symptoms. Anticholinergic drugs (eg, hyoscyamine 0.125 mg orally 30 to 60 minutes before meals) may be used for their antispasmodic effects.
In patients with constipation-predominant IBS (IBS-C), the chloride channel activator lubiprostone 8 mcg or 24 mcg orally twice a day and the guanylate cyclase C agonists linaclotide 72 mcg, 145 mcg, or 290 mcg orally once a day or plecanatide 3 mg orally once a day may be helpful. Polyethylene glycol laxatives have not been well-studied in IBS. However, they have been shown to be effective for use in chronic constipation and for bowel lavage before colonoscopy and are thus frequently used for IBS-C. Prucalopride is a highly selective serotonin receptor agonist that is approved for chronic constipation.
In patients with diarrhea-predominant IBS (IBS-D), oral diphenoxylate 2.5 to 5 mg or loperamide 2 to 4 mg may be given before meals. The dose of loperamide should be titrated upward to reduce diarrhea while avoiding constipation. Rifaximin is an antibiotic that has been shown to relieve symptoms of bloating and abdominal pain and to help decrease looseness of stools in patients with IBS-D. The recommended dose of rifaximin for IBS-D is 550 mg orally 3 times a day for 14 days. Alosetron is a 5-hydroxytryptamine (serotonin) 3 (5HT3) receptor antagonist that may benefit women with severe IBS-D refractory to other drugs. Because alosetron has been associated with ischemic colitis, its use in the US is under a restricted prescribing program. Eluxadoline has mixed opioid receptor activity and is indicated for treatment of IBS-D; however, because of the risk of pancreatitis, it cannot be used in patients who have had a cholecystectomy, have sphincter of Oddi dysfunction, have liver disease, or drink more than 3 alcoholic drinks a day.
For many patients, tricyclic antidepressants (TCAs) help relieve symptoms of diarrhea, abdominal pain, and bloating. These drugs are thought to reduce pain by down-regulating the activity of spinal cord and cortical afferent pathways arriving from the intestine. Secondary amine TCAs (eg, nortriptyline, desipramine) are often better tolerated than parent tertiary amines (eg, amitriptyline, imipramine, doxepin) because of fewer anticholinergic, sedating antihistaminic, and alpha-adrenergic adverse effects. Treatment should begin with a very low dose of a TCA (eg, desipramine 10 to 25 mg orally once a day at bedtime), increasing as necessary and tolerated up to about 100 to 150 mg orally once a day.
Selective serotonin reuptake inhibitors are sometimes used in patients with anxiety or an affective disorder, but studies have not shown a significant benefit for patients with IBS and they may exacerbate diarrhea.
Preliminary data suggest that certain probiotics (eg, Bifidobacterium infantis) alleviate IBS symptoms, particularly bloating. The beneficial effects of probiotics are not generic to the entire species but specific to certain strains. Certain aromatic oils (carminatives) can relax smooth muscle and relieve pain caused by cramps in some patients. Peppermint oil is the most commonly used agent in this class.
Psychologic therapies
Cognitive-behavioral therapy, standard psychotherapy, and hypnotherapy Hypnotherapy Hypnotherapy, a type of mind-body medicine, is derived from western psychotherapeutic practice. Patients are put into an advanced state of relaxation and focused concentration to help them improve... read more may help some IBS patients.
Key Points
IBS is recurrent abdominal discomfort or pain accompanied by ≥ 2 of the following: pain that is related to defecation, change in frequency of stool (diarrhea or constipation), or change in consistency of stool.
Etiology is unclear but appears to involve both physiologic and psychosocial factors.
Exclude more dangerous diseases by testing, particularly in patients with red flag findings, such as older age, fever, weight loss, rectal bleeding, or vomiting.
Common illnesses that may be confused with IBS include lactose intolerance, drug-induced diarrhea, post-cholecystectomy diarrhea, laxative abuse, parasitic diseases, eosinophilic gastritis or enteritis, microscopic colitis, small-bowel bacterial overgrowth, celiac disease, and early inflammatory bowel disease.
Typical testing to consider includes complete blood count, biochemical profile (including liver tests), serologic markers for celiac disease, stool examination for infection (in patients with diarrhea predominance), thyroid-stimulating hormone and calcium (for patients with constipation), and flexible sigmoidoscopy or colonoscopy.
A supportive, understanding, and therapeutic relationship is essential; direct drug therapy toward the dominant symptoms.
More Information
The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
American Gastroenterological Association: Guidelines on the laboratory evaluation of functional diarrhea and diarrhea-predominant irritable bowel syndrome in adults (IBS-D)
American College of Gastroenterology: Monograph on management of irritable bowel syndrome
American Gastroenterological Association: Technical review and guideline on pharmacologic management of irritable bowel syndrome
National Institute of Diabetes and Digestive and Kidney Diseases: Useful dietary advice for patients about eating, diet, and nutrition for IBS
