Irritable Bowel Syndrome: Pathophysiology and Goals of Therapy



  • Summary:

    Dr. Mark Pimentel from the GI Motility Program, Cedars-Sinai Medical Center moderated the topic "Irritable Bowel Syndrome: Pathophysiology and Goals of Therapy" with Drs. Brooks Cash from the Walter Reed National Military Medical Center, Anthony Lembo from GI Motility Laboratory, Beth Israel Deaconess Medical Center Division of Gastroenterology, and Harvard Medical School, and Phil Schoenfeld of the University of Michigan School of Medicine, Ann Arbor, MI.

    The discussion focused primarily on:

    1. The major symptoms and prevalence of irritable bowel syndrome (IBS);
    2. the criteria for the diagnosis of IBS;
    3. the major categories of IBS;
    4. the pathophysiology of and mechanisms hypothesized to underlie IBS;
    5. the impact of IBS on the quality of life;
    6. the relationship between IBS and other gastrointestinal disorders;
    7. indications for further testing of IBS patients; and
    8. current and future treatments for IBS and their efficacy.

    Med Roundtable Gen Med Ed. 2014;1(3):248–256.

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DR. PIMENTEL: I’m Mark Pimentel, Director of GI Motility at Cedars-Sinai Medical Center in Los Angeles. I am joined today by Brooks Cash from the Walter Reed National Military Medical Center in Bethesda, Maryland; Anthony Lembo, Director of the GI Motility Laboratory at Beth Israel Deaconess Medical Center, Division of Gastroenterology; and Associate Professor of Medicine at Harvard Medical School in Boston, Massachusetts; and Phil Schoenfeld, Associate Professor of Medicine and Director of the GI Epidemiology Training Program at the University of Michigan School of Medicine in Ann Arbor. Our topic for this roundtable is irritable bowel syndrome (IBS), a condition for which we’ve recently observed many exciting developments, as recent as in the last week. To begin, I’d like to ask Dr. Lembo to discuss the prevalence of IBS in the general population and by sex.

DR. LEMBO: IBS is a very common disorder, with an estimated prevalence of 10% to 15% in the general population of the United States. At least some of the variation in IBS prevalence is due to the use of different criteria in its diagnosis, as well as differences in the populations examined and the specific questions used to elicit information from them when estimating its prevalence. Generally, women tend to complain of IBS symptoms twice as often as men do, and a greater number of relatively younger adults present with IBS symptoms compared to older adults.

DR. PIMENTEL: Some say that, in India, for example, the prevalence of IBS is not as high, while others say that more men than women have IBS in some developing countries. Do you think that these differences between developed and developing nations can be attributed to a relative lack of research on IBS in developing countries?

DR. SCHOENFELD: Yes. Differences in the prevalence of IBS among countries most likely reflect differences in the way studies are designed. Additionally, health care-seeking behaviors may differ across cultures, which may influence the reporting of the data regarding the prevalence of these disorders in men and women. For example, epidemiologic data indicate that women are more likely than men to seek health care in the United States.

DR. PIMENTEL: Quality of life is a particular consideration with this disease. How does IBS compare to other disease states, such as diabetes and heart disease, in this respect?

DR. CASH: IBS has been shown to have a significant negative impact on the quality of life, with some data suggesting that the quality-of-life impairment of IBS patients is similar to that of patients on chronic renal dialysis or those with major depression. Patients with IBS are known to have additional non-gastrointestinal (GI)-associated somatic complaints such as fibromyalgia or interstitial cystitis symptoms that lower their health-related quality of life. In fact, a recent review of articles published over the last decade identified 31 comorbid conditions and 24 concomitant symptoms only in patients with IBS with constipation (IBS-C). The most common comorbid conditions identified in this review included functional dyspepsia, depression, small intestinal bacterial overgrowth, food intolerances, and urinary disorders.1

DR. PIMENTEL: One thing that I notice—and talk to my patients about—is the lack of attention to IBS compared to Crohn’s disease and other GI disorders. While I wouldn’t wish Crohn’s disease on anybody, its course is very predictable. Every day, Crohn’s disease patients wake up in the morning, and have 6 bowel movements; they know what their day is going to be like and can plan accordingly. IBS patients do not have such certainty; they don’t know whether they’re going to have a bowel movement and, if so, if it’s going to be diarrhea. They don’t even know if they’re going to be doubled over in pain during a meeting in the middle of the day. The unpredictability of IBS and its symptoms really affect the quality of life more than we give it credit for, in comparison to diseases that may have a greater impression on the doctor because they are associated with inflammation. Dr. Lembo, do you think that we are expending enough effort to demonstrate the importance of IBS to the medical community?

DR. LEMBO: I think we need to do a better job because, as we all know from our patients, the impact of IBS on quality of life can be significant. Studies have shown that patients with IBS have quality-of-life scores similar to or worse than patients with congestive heart disease and dialysis-dependent kidney failure.2

I agree that the lack of predictability of bowel function and the severity of abdominal pain are big factors in lowering an IBS patient’s quality of life. In this respect, IBS patients certainly differ from patients with other GI disorders such as celiac disease, for whom pain may not be a predominant feature. Patients with IBS also often find bloating to be quite difficult to deal with, not only because of the associated discomfort but also because of its effect on their appearance. Therefore, I think there are multiple factors reducing IBS patients’ quality of life, including the lack of predictability of bowel movements, abdominal pain, and bloating.

DR. PIMENTEL: That segues us into diagnosis. We’ve developed these criteria, and we’ve subcategorized IBS into diarrhea, constipation, and mixed forms of IBS. Dr. Cash, can you take us through these criteria and explain why, based upon them, we’ve developed these different categories of IBS?

DR. CASH: A number of different criteria have been devised to try and help diagnose, and then subsequently categorize IBS. One reason for their development is that there is no biomarker for IBS diagnosis; it’s almost entirely a clinically based, symptom-based diagnosis.

After the development of the first set of criteria, referred to as the Manning criteria,3 the Rome Committee on Functional and GI Disorders issued several iterations of its own set of criteria, the most current of which is the Rome III criteria.4 One reason for the development of these criteria was to categorize patients with IBS symptoms into similar groups to encourage research so that, for example, researchers conducting a therapeutic study of an agent for IBS could identify patients with similar symptoms for enrollment in a study.

The Rome III criteria established 3 major categories and 1 somewhat minor category of IBS: (1) IBS-C, (2) IBS with diarrhea (IBS-D), (3) mixed-bowel habit IBS, and (4) unsubtyped IBS (IBS-U). These criteria are based on the predominant stool form, and patients with IBS-D have soft, mushy, or loose, watery stool at least 25% of the time and don’t have constipated, hard, or scybalous-type stool more than 25% of the time.

On the other end of the spectrum, patients with IBS-C have a constipated form of stool at least 25% of the time and do not have diarrhea more than 25% of the time. The mixed pattern is somewhere in between, and IBS-U doesn’t necessarily fit any of those categories.

The Rome criteria were developed for application in clinical research, but many clinicians have applied them to their clinical practice. The diagnosis of IBS is based on, at least with the current Rome III criteria, the presence of at least 2 of the 3 major features associated with the abdominal pain or discomfort attributed to alternations in bowel habits.

The first is that patients have some relief with regards to their abdominal pain or discomfort with defecation, either completely or partially. The second is that the abdominal pain or discomfort should be associated with a change in the form of the stool. The third feature is that the abdominal pain or discomfort should be associated with a change in the frequency of the stool. Not all patients presenting with those symptoms will be diagnosed with IBS, including a small number who fulfill the criteria for diagnosis of organic disease. Many clinicians still consider IBS a diagnosis of exclusion for explaining GI symptoms, despite good evidence of the validity of the Rome criteria in the absence of alarming features.

DR. PIMENTEL: How good are these criteria, Dr. Lembo? Can they be used clinically and/or are they sufficiently reliable to negate the need for testing?

DR. LEMBO: It’s hard to answer how good these criteria are because it’s a consensus definition. As Dr. Cash mentioned, the reason for devising them was to have some uniformity for both clinical as well as research purposes. To that extent, I think they serve an important purpose, but as they’re not based on a pathophysiological mechanism, they overlap with the criteria for other diseases.

DR. PIMENTEL: Do we need testing? One of the other things that was mentioned, bloating, is a missing piece of the Rome criteria, which is also a problem that all 4 of us have discussed.