DEFINITION

IBS is defined on the basis of the recently modified Rome III criteria as recurrent abdominal pain or discomfort at least 3 days per month in the last 3 months that started at least 6 months before diagnosis, cannot be explained by a structural or biochemical abnormality, and is associated with at least two of the following: improvement with defecation, onset associated with a change in frequency of stool, and onset associated with a change in form (appearance) of stool.¹ Other symptoms that support the diagnosis but are not part of the criteria include abnormal stool frequency (≤3 bowel movements per week or >3 bowel movements per day), abnormal stool form (lumpy/hard or loose/watery), defecation straining, urgency, or feeling of incomplete bowel movement, passing mucus, and bloating. Four possible IBS subtypes include IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M) and un-subtyped IBS depending on the predominant stool pattern.²

PREVALENCE

IBS is one of the most commonly diagnosed gastrointestinal (GI) conditions and also one of the most common functional GI disorders seen in clinical practice.³ Estimates of prevalence vary, largely because of the differences among epidemiologic studies (e.g., the use of different diagnostic criteria, population selection, and data sources). Approximately 10% to 20% of the general adult population has reported symptoms compatible with IBS.^4,⁵ However, only 15% of those affected actually seek medical attention.^5,⁶ IBS accounts for 12% of primary care patients and 28% of gastroenterology practice patients (41% of all functional GI disorders).⁶ Patients often experience the onset of symptoms as young adults, but the prevalence is similar in older adults. IBS is diagnosed in women more than twice as often as men; however, studies have found the prevalence of pain-related symptoms of IBS to be equal among men and women and the prevalence of symptoms not related to pain, such as constipation, bloating and extra-intestinal manifestations, to be greater among women.⁷

The financial burden of IBS is high, both in direct and indirect costs.⁸ IBS has a major impact on the quality of life of those afflicted, affecting social interactions and professional opportunities.⁹

PATHOPHYSIOLOGY

To date, no physiologic mechanism unique to IBS has been identified. Rather, it is currently viewed as a biopsychosocial disorder resulting from an interaction among a number of factors: visceral hyperalgesia, genetic and environmental factors, infection, inflammation, gut motility, and psychological factors ¹⁰ Dietary factors, GI dysmotility dysfunction, and the role of gut flora are evolving mechanisms.

Visceral Hypersensitivity

Many studies have shown that in patients with IBS, both awareness and pain caused by balloon distention in the large and small bowel are experienced at significantly lower balloon volumes than those reported by healthy subjects.¹¹^–¹³ It is not known at which level of pain-signal transmission (starting at the receptor in the gut wall, through the spinal cord to the brain) this increased sensitivity is expressed, but it is selective to visceral stimuli, because patients with IBS have normal or even decreased sensitivity to somatic stimuli.^14,¹⁵

Abnormal Gut Motility

The changes in gut motility observed in IBS are qualitative, with no distinct pattern that can distinguish patients from healthy subjects. Two major changes are observed: Changes in gut transit and increased motility. Enhanced gut transit is seen in some patients with diarrhea-predominant IBS, and decreased gut transit is seen in some patients with constipation-predominant IBS. Increased motility compared with healthy subjects is seen in response to various stimuli, such as psychological stress, meals, and balloon inflation in the gut.¹⁰

Psychosocial Factors

IBS has long been dismissed as a psychosomatic condition because it has no clear cause or pathophysiology. Psychological stress and emotional events, such as physical or sexual abuse, can result in GI symptoms in healthy subjects, but they affect patients with IBS to a greater degree. The common psychological symptoms associated with IBS are depression, somatization, anxiety, hostility, phobia, and paranoia. Up to 50% of patients with IBS meet criteria for a psychiatric diagnosis as compared with an average of 20% with organic GI disorders and 15% of control subjects.¹⁰ Although there are no psychological or psychiatric disorders specific to IBS, identification of such disorders can help in planning psychological or psychopharmacologic treatment.

Brain-Gut Interaction

The central nervous system (CNS) modulates various functions such as secretion, motility, and blood flow.¹⁶ Signals from the gut, in turn, are involved in regulating reflexes. Perception of events in the gut involves activation of afferent pathways, with information being modulated at different levels, peripheral as well as central.¹⁷ A major advance in our understanding of brain-gut interaction and its alteration in IBS occurred with the introduction of functional magnetic resonance imaging (MRI). This technique allowed assessment of the difference in cortical function in response to gut stimulation between healthy subjects and IBS patients,¹⁸ opening the door for potential pharmacologic and behavioral interventions.

Latent or Potential Celiac Disease

The concept of latent or potential celiac disease has recently been introduced into the pathogenesis of IBS. Abdominal symptoms in the absence of mucosal abnormalities are features of IBS and latent or potential celiac disease.¹⁹ In a study of genetic, serologic, and histologic markers of celiac disease in 102 patients with diarrhea-predominant IBS, 35% of the patients had positive findings for human leukocyte antigen (HLA)-DQ2, 23% had increased intraepithelial lymphocyte counts, and 30% had increased celiac disease–associated antibodies in the duodenal aspirates, including antibodies against gliadin, tissue transglutaminase, β-lactoglobulin, and ovalbumin.¹⁹ Stool frequency and the intestinal immunoglobulin A (IgA) level decreased significantly under a gluten-free diet in a subgroup of IBS patients with positive HLA-DQ2 and positive intestinal celiac disease–associated antibodies when compared with IBS patients without these markers.¹⁹ Celiac disease–associated IgG and HLA-DQ2 expression can identify likely responders to gluten-free diet in patients with IBS-D (diarrhea predominant IBS).²⁰

Infection and Inflammation

Clinical, epidemiologic, and physiologic studies have shown that acute, transient GI infection is associated with a syndrome that often meets diagnostic criteria for the diagnosis of IBS. This was observed after documented outbreaks of enteric infections with organisms such as Campylobacter jejuni or Salmonella.^21,²² IBS and small intestine bacterial overgrowth might share similar symptoms. In a study of 202 patients with IBS, 157 (78%) had small bowel bacterial overgrowth. Intraepithelial lymphocytes, lamina propria CD3 and CD25 cells, neutrophils, and mast cells are increased in patients with IBS.²³

The exact mechanisms whereby the inflammatory changes cause the symptoms are not clear. The inflammatory response may be associated with activating enterochromaffin cells to produce 5-hydroxytryptamine (5-HT) and CD3 cells to produce cytokines, which in turn leads to enhanced motility, increased intestinal permeability, and lowered visceral sensation thresholds.²⁴ In one prospective study of postinfectious IBS, it was found that patients whose symptoms remained 3 months after an enteric infection not only had increased mucosal cellularity but also had increased psychosocial distress at the time of the infection. Lowered visceral sensation thresholds and increased motility were present after the infection, regardless of whether or not the symptoms remained.²⁵ Therefore, in patients with IBS refractory to a gluten-free diet, small bowel bacterial overgrowth may be suspected, and prompt hydrogen breath testing may be warranted.

Fructose and Lactose Intolerance

Common symptoms of dietary fructose and lactose intolerance include bloating, flatulence, pain, and diarrhea which have also been found in patients with unexplained dyspepsia or functional bowel disorders such as IBS. It has been shown that approximately one third of patients with suspected IBS might also have fructose intolerance as identified by a positive fructose breath test. Although there are no data documenting the efficacy of a fructose-restricted diet, a study of 80 suspected IBS patients showed significant relief of symptoms in those who were compliant with a fructose-restricted diet.²⁶ Patients with IBS have subjectively reported higher incidence of lactose intolerance, but it is hard to tell whether reported symptoms are secondary to lactose intolerance or IBS in the absence of documented lactose malabsorption. A period of avoiding dairy products or requesting a test for lactose malabsorption (or both) may be beneficial in this area.

SIGNS AND SYMPTOMS

Patients with IBS can present with a wide variety of GI and extraintestinal symptoms. However, the symptom complex of chronic abdominal pain and altered bowel habits that cannot be explained by identifiable structural or biochemical abnormalities is the main clinical pattern of IBS.

Chronic abdominal pain in IBS is usually described as a crampy sensation, with varying intensity and periodic exacerbation. The pain is generally located in the lower abdomen, although the location and character of the pain can also vary. Emotional stress and eating can exacerbate the pain, whereas defecation often provides some relief. Progressive pain that awakens the patient from sleep or prevents sleep should prompt a search for causes other than IBS.

Because the range of normal bowel habits is broad, a careful history should include the volume, frequency, and consistency of the patient’s stool. Assuming no use of laxatives or antidiarrheals, subtyping of IBS by predominant stool pattern has been divided into the following: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), mixed IBS (IBS-M) and unsubtyped IBS. The frequency of bowel movements in normal persons is variable, and it can range from three times a day to three times a week. Patients with IBS complain of diarrhea, constipation, alternating diarrhea and constipation, or normal bowel habits alternating with diarrhea or constipation reflecting intestinal transit time.²

Irritable Bowel Syndrome with Diarrhea

Diarrhea is generally characterized as a condition of at least 25% frequent loose stools of small and moderate volume without abdominal comfort in at least 75% of stools ² or Bristol Stool Form Scale 6-7 (fluffy pieces with ragged edges, a mushy stool or watery, no solid pieces, entirely liquid). In addition, hard and lumpy stool typically occurs in less than 25% of bowel movements. Bowel movement generally occurs during waking hours, most often in the morning or after meals. Most bowel movements are preceded by urgency and may be followed by a feeling of incomplete evacuation. Pseudodiarrhea—frequency defecation and urgency without solid stools—is not considered diarrhea.²⁷ Nocturnal diarrhea, bloody stools, dehydration, or weight loss are not features of IBS.

Irritable Bowel Syndrome with Constipation

Constipation can last from days to months, with interludes of diarrhea or normal bowel function. Stools are often hard and may be described as pellet shaped in at least 25% of bowel movements, or Bristol Stool Form Scale 1-2 (separate hard lumps like nuts that are difficult to pass, or sausage shaped but lumpy). In addition, loose (mushy) or watery stools account for less than 25% of bowel movements. Patients might also experience a sense of incomplete evacuation, even when the rectum is empty. This can lead to straining with defecation, prolonged time on the toilet, and inappropriate use of enemas or laxatives.

Mixed Irritable Bowel Syndrome

Mixed IBS is defined as hard or lumpy stool at least 25% of bowel movements and loose or mushy stools at least 25% of bowel movements using Bristol scale 1-2 for constipation and scale 6-7 for diarrhea.

Unsubtyped Irritable Bowel Syndrome

Unsubtyped IBS is defined as insufficient abnormality of stool consistency to meet criteria for IBS-D, IBS-C or IBS-M.

Other Gastrointestinal Symptoms

Upper GI symptoms are not uncommon in patients with IBS. These include symptoms of heartburn, dysphagia, nonulcer dyspepsia, nausea, and noncardiac chest pain.²⁸ Patients with IBS often complain of abdominal bloating and increased gas production in the form of flatulence or belching.

Extraintestinal Symptoms

Patients with IBS have a high frequency of non-GI symptoms, including rheumatologic symptoms, headache, genitourinary symptoms such as urinary frequency and urgency, dyspareunia, sexual dysfunction, and sleep-related disturbances.²⁹

ACTIVE DIAGNOSIS

A diagnosis is based on identifying positive symptoms consistent with IBS and excluding other conditions with similar clinical presentations in a cost-effective manner. In the absence of biologic markers, attempts have been made to standardize the diagnosis of IBS using symptom-based criteria. These include criteria proposed by Manning and colleagues in 1978 ³⁰ and the international workshop criteria, Rome I and II, with the updated current Rome III criteria.¹ In the criteria of Manning and associates,¹ the symptoms associated with IBS included relief of pain with bowel movements, looser and more frequent stools with onset of pain, passage of mucus, and a sense of incomplete evacuation. The current Rome III criteria, described earlier, are a simplification of the Rome II criteria—for example, by using stool form as a criterion. A key feature of the Rome III definition is the presence of abdominal discomfort or pain.

The diagnostic evaluation of patients with IBS can be challenging. It is generally agreed that the initial diagnosis of IBS can be fulfilled by the following: symptom-based diagnostic criteria are met, such as Rome III; negative results are obtained on physical examination; and a cost-effective, conservative set of screening studies has been performed. It is important to exclude organic causes of symptoms compatible with IBS. However, to avoid unnecessary and costly testing, the diagnosis of IBS should not be made simply by excluding organic disorders. Emphasis should be placed on identifying a symptom complex compatible with IBS and then using prudent, although not exhaustive, testing to make a positive diagnosis. The Rome and Manning criteria provide guidelines to identify patients with suspected IBS.

In 2002, the American Gastroenterological Association (AGA) published an extensive review and position statement ⁶ regarding pathophysiology, role of psychosocial factors, diagnosis, and treatment of IBS, and in April 2006, the Rome III criteria were again modified to include the IBS bowel habit subgroups that emphasized the use of the stool consistency as outlined in April 2006 Gastroenterology. It has been acknowledged that evidence exists for a diagnostic and treatment approach based on the predominant symptom, its severity, and associated psychosocial features, although more studies are needed to understand the mechanism underlying these symptoms and to develop effective treatments (Box 1).

Box 1 Stepwise Approach to Irritable Bowel Syndrome