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Evidence-Based Management of Irritable Bowel Syndrome With Diarrhea
Mark Pimentel, MD

Evidence-Based Management of Irritable Bowel Syndrome With Diarrhea

Mark Pimentel, MD
Irritable bowel syndrome (IBS), a complex disorder of the gastrointestinal tract, is characterized by abdominal pain associated with defecation or changes in stool form or frequency. IBS is associated with substantial burden, including direct medical costs and indirect costs. Direct costs associated with IBS in the United States have been estimated to exceed $1 billion. However, indirect costs, such as negative effect on quality of life (QOL) and work productivity, are difficult to quantify. There are 3 main subtypes: IBS with prominent diarrhea (IBS-D), IBS with constipation, and IBS with mixed symptoms of both constipation and diarrhea. A number of pharmacologic agents have been used to treat IBS-D despite lack of approval by the FDA for this indication. The pharmacologic agents that are indicated by the FDA for the treatment of IBS-D include alosetron, eluxadoline, and rifaximin. The negative impact of IBS-D symptoms on QOL reported by patients indicate there is an unmet need for therapies that effectively treat and manage the symptoms of this condition. Addressing gaps in treatment is an important priority.
Am J Manag Care. 2018;24:-S0
Irritable bowel syndrome (IBS) is a chronic, potentially disabling disorder of the gastrointestinal (GI) tract with a relapsing/remitting course in which abdominal pain is associated with defecation or changes in stool form or frequency.1-3

Diagnosis of IBS

The Rome IV criteria represent the current standard for diagnosing IBS. In 2016, the Rome III criteria were updated by a group of multinational experts in functional GI disorders.2,3 The most significant change from the Rome III criteria is the elimination of the term “discomfort” from the definition, as it is vague.3

The current diagnostic criteria for IBS include abdominal pain at least 1 day per week during the last 3 months that is associated with at least 2 of the following3:


Change in stool frequency

Change in stool form (ie, appearance)

To receive a diagnosis of IBS, individuals must have symptoms meeting the diagnostic criteria for 3 months, with the onset of initial symptoms at least 6 months before diagnosis.3

The diagnosis of IBS should be based on a clinical evaluation of the patient, a physical examination, and laboratory tests (minimal) and, when clinically indicated, a colonoscopy or other appropriate tests.3 The clinical evaluation includes determining the presence of abdominal pain, assessing bowel and dietary habits, and the patient’s medical and surgical history.2,3

The presence of abdominal pain is required for a diagnosis of IBS. Pain usually occurs in the lower abdomen but can occur anywhere in the abdomen.3 The presence of disordered bowel habits is also required for a diagnosis of IBS.2 Disordered bowel habits include a history of constipation and/or diarrhea. The association of constipation and/or diarrhea with abdominal pain should be determined.3 Abdominal bloating is not required for a diagnosis of IBS but is often present and can support the diagnosis.2

Physical examination in patients with IBS usually reveals abdominal tenderness but rarely other abnormalities. Physical examination should include a digital rectal examination, particularly in patients with constipation. The presence of enlarged liver, spleen, or lymph nodes; ascites; or a mass suggests a condition other than IBS.2 A normal physical examination and the absence of warning signs (see Differential Diagnosis section below) in the patient’s history support using the Rome IV diagnostic criteria to confirm a diagnosis of IBS.2

Patients with IBS generally experience symptoms for extended periods before they receive a diagnosis. Individuals who have not yet been given a diagnosis of IBS may have an even greater burden of symptoms than those who have received a definitive diagnosis.4 There are several reasons for a delayed diagnosis of IBS. Not all individuals with IBS symptoms consult a physician about their symptoms; in the United States, 30% of individuals with symptoms of IBS do so, and of these, 80% have IBS with prominent diarrhea (IBS-D). Those who see a physician have symptoms similar to those who do not but have higher pain scores, more anxiety, and poorer quality of life (QOL).5

Although the Rome guidelines clearly define IBS, 72% of community providers (community nonexpert gastroenterologists, general internal medicine physicians, and nurse practitioners) consider IBS a diagnosis of exclusion, whereas just 8% of experts (IBS key opinion leaders) do. This shows a clear disconnect between academic guidelines and community practice. Those who believe IBS is a diagnosis of exclusion are more likely to order additional diagnostic tests than those who do not.6

Classification of IBS

IBS is classified into subtypes based on symptoms. Although subtyping is used to suggest treatment, it is thought that each subtype may include more than 1 disease entity, explaining the variable responses to treatment.2 The diagnostic criteria used to define the IBS subtypes are the predominant bowel habits based on stool form on days with at least 1 abnormal bowel movement.3

The Bristol Stool Form Scale (BSFS) is used to record stool consistency on days when patients are experiencing abnormal bowel habits and defines the following 7 types3:

Type 1: separate hard lumps, like nuts; hard to pass

Type 2: sausage-shaped but lumpy

Type 3: like a sausage but with cracks on the surface

Type 4: like a sausage or snake, smooth and soft

Type 5: soft blobs with clear-cut edges

Type 6: fluffy pieces with ragged edges, a mushy stool

Type 7: watery, no solid pieces, entirely liquid

To accurately classify the subtype of IBS based on bowel habit abnormalities using the BSFS, patients should not be taking any medications to treat their symptoms, including laxatives or antidiarrheal agents, during the period of evaluation. IBS subtyping is most accurate when patients experience abnormal bowel habits at least 4 days per month.3

The IBS subtypes comprise 3 classifications based on the predominant bowel disorder and include IBS-D, IBS with constipation (IBS-C), and IBS with mixed symptoms of constipation and diarrhea (IBS-M).3 Individuals with a diagnosis of IBS whose bowel habits cannot be classified as IBS-D, IBS-C, or IBS-M are considered to have unclassified IBS (IBS-U).Frequent changes in diet or medications or the inability to discontinue GI medications may interfere with accurate determination of IBS subtype.3

The IBS-D subtype is defined as follows: More than 25% of bowel movements using the BSFS are type 6 or 7, and less than 25% of bowel movements are type 1 or 2. Alternatively, for epidemiologic studies and in clinical practice, if the patient reports abnormal bowel movements that are usually diarrhea, the patient can be considered to have IBS-D.3 Experiencing bowel patterns with at least 3 different types of stool in a week also supports a diagnosis of IBS-D.3

The IBS-C subtype is defined as follows: More than 25% of bowel movements are type 1 or 2 using the BSFS, and less than 25% are type 6 or 7. Alternatively, for epidemiologic studies and in clinical practice, if the patient reports abnormal bowel movements that are usually constipated, the patient can be considered to have IBS-C.3

The IBS-M subtype is defined as follows: More than 25% of bowel movements using the BSFS are types 1 and 2, and more than 25% are types 6 and 7. Alternatively, for epidemiologic studies and in clinical practice, if the patient reports abnormal bowel movements that are usually both constipation and diarrhea, the patient can be considered to have IBS-M.3

Patients who have the IBS-U subtype meet the diagnostic requirement for IBS, but their bowel habits cannot be accurately categorized as IBS-D, IBS-C, or IBS-M.3

Differential Diagnosis

IBS is not a diagnosis of exclusion.However, IBS shares symptoms with other conditions that should be ruled out during diagnosis. Warning signs that suggest a diagnosis of a condition other than IBS are also known as “alarm” features or red flag symptoms. Alarm features include fever; weight loss; waking during the night as a result of GI symptoms; blood in the stool (including occult blood); family history of colon cancer or inflammatory bowel disease (IBD); recent use of antibiotics; newly onset, progressive symptoms; and onset of symptoms after age 50 years.7

A limited number of laboratory tests may be conducted to identify conditions other than IBS in patients,3 including a complete blood count. Thyroid tests may be appropriate for some patients.3 Stool tests for bacteria and parasites or their eggs may be warranted in areas where infectious causes of diarrhea are common.3

Bacteria that cause acute gastroenteritis, a known precipitant of IBS-D, produce cytolethal distending toxin B (CdtB). Circulating antibodies to CdtB (anti-CdtB) also cross-react with the intestinal protein vinculin. Titers of anti-CdtB and anti-vinculin are elevated in individuals with IBS-D compared with healthy individuals or those with celiac disease and can therefore be used as biomarkers for IBS-D.8 Celiac disease can also be distinguished via other serologic tests and confirmational duodenal biopsy.3

Serum C-reactive protein and fecal calprotectin can be used to rule out IBD in patients with typical IBS symptoms. However, the erythrocyte sedimentation rate and fecal lactoferrin are not useful for ruling out IBD in patients with IBS.9

Screening colonoscopy is warranted in patients 50 years or older, African Americans 45 years and older, patients who have a family history of colorectal cancer, those with persistent diarrhea that has not responded to empiric therapy, and those with alarm signs of other disorders.2 These recommendations are identical to the national recommendations for the general population.2

Epidemiology of IBS

In a meta-analysis of 10 studies (N = 52,790), the pooled prevalence of IBS in the United States was estimated to be 11.8% (95% CI, 7.4%-17.2%).1 IBS is reported more frequently in women than in men and in individuals aged 30 to 49 years compared with those 50 years and older.1 In another meta-analysis of 14 studies of patients with IBS, the prevalence of IBS-D was highest, accounting for 40.0% of the patient population (95% CI, 31.0%-48.0%); the prevalence of IBS-C was 35.0% (95% CI, 29.0%-41.0%); and the prevalence of IBS-M was 23.0% (95% CI, 15.0%-31.0%).1

Pathophysiology of IBS

IBS is a complex disorder with a pathophysiology3 that is not completely understood.10 Risk factors for IBS in susceptible individuals include a genetic predisposition to the condition, exposure to environmental factors, and psychosocial factors (eg, an abnormal stress response).3

The onset or exacerbation of IBS symptoms can be caused by previous gastroenteritis, food intolerances, chronic stress, diverticulitis, or surgery.3

IBS symptoms may be caused by altered intestinal permeability resulting from infections, inflammation, or changes in the gut microbiome, all of which can trigger a release of inflammatory mediators such as cytokines or chemokines. These inflammatory mediators could lead to changes in the central nervous system that result in new onset of anxiety and depression; this, in turn, can further exacerbate IBS symptoms in a feedback loop.2 About half of IBS cases originate in the gut rather than the brain, and psychological stress develops after IBS symptoms.2

IBS-like symptoms are known to persist in 10% to 20% of individuals who have had acute bacterial, protozoan, or viral gastroenteritis and can be associated with intestinal inflammation. More than 30% of individuals who have experienced gastroenteritis develop IBS-D, which is referred to as postinfectious IBS (PI-IBS).10 The pathophysiology of PI-IBS is thought to be different from that resulting from other causes.2 Viral gastroenteritis is less apt to lead to PI-IBS than bacterial enteritis or protozoan or helminthic infections.11

Clinical Burden and QOL Associated With IBS

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