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Keywords:

  • alarm features;
  • biomarkers;
  • diagnosis;
  • diagnostic criteria;
  • irritable bowel syndrome;
  • Kruis;
  • Los Angeles/IBS;
  • Manning;
  • Rome

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

There are a number of reasons to establish the accurate diagnosis of irritable bowel syndrome (IBS): to relieve patient uncertainty; to avoid adverse effects of unnecessary medications or treatments; to avoid unnecessary diagnostic procedures and surgeries; to conserve limited healthcare resources; and, of course, to initiate the most appropriate treatment. However, making the diagnosis of IBS remains difficult because it is clinically heterogeneous, no biological marker to detect it exists, many other diseases share the same clinical manifestations and it is often difficult for both physicians and patients to accept the uncertainty of a symptom-based diagnosis. Different diagnostic criteria have been developed during the last 4 decades but none have proved to be an ideal method of accurately diagnosing IBS. Just as importantly, physicians are frequently unaware of published guidelines or consciously ignore these diagnostic criteria. Most clinicians still believe IBS is a diagnosis of exclusion and not a positive diagnosis based on history, physical examination, use of published diagnostic criteria such as the Rome III criteria, and the absence of alarm features. In the sections to follow we will address the inherent difficulties of diagnosing IBS, highlight the importance of symptom-based diagnoses to help reign in soaring healthcare costs, and discuss future strategies that may enable a more cost-efficient diagnosis of IBS.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

Irritable bowel syndrome (IBS) is a very common medical condition. The prevalence of IBS varies among countries due in part to the use of different criteria used to define it; the pooled global prevalence has been estimated at 11%.1,2 Irritable bowel syndrome obviously affects patients physically; however, it also affects them psychologically, socially, and economically. The economic impact of IBS is worth highlighting because patients with IBS consume over 50% more healthcare resources than matched controls without IBS.3

Irritable bowel syndrome is a complex and controversial disorder: symptoms are non-specific, patients are heterogeneous, and the evaluation and management of IBS varies dramatically from provider to provider. Some physicians, whether gastroenterologists or general practitioners, believe that IBS is a distinct functional bowel disorder well defined using the biopsychosocial model. Others view IBS as a mixture of different diseases, most of which (if not all) are organic in nature; they believe that in the future these organic causes will be identified and IBS as a diagnostic entity will disappear. Finally, there is also a group of professionals who do not believe that IBS exists at all, and they defend their view by stating that “these symptoms are normal and patients should cope with them as they are not a medical priority.” Thus, there are believers, skeptics, non-believers, and agnostics all involved in the evaluation and treatment (or non-treatment in some cases) of millions of IBS patients desperately searching for answers and symptom relief. Adding to the complexity of this situation is the need for physicians to be confident in their diagnosis of IBS?

Making a positive diagnosis of IBS has several important implications: to reassure the patient; to make him or her feel confident about future decisions; to direct treatment and use resources in a logical manner; and also to possibly minimize physicians’ concerns. The last point is not the most important one; making medical decisions has always (ALWAYS) carried some risk. The key issue is how to obtain a certain diagnosis of IBS while minimizing risks, all at a reasonable cost.

Why making a diagnosis of IBS is so important

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

Making a diagnosis of IBS is important because of the following reasons, among others. Firstly, millions of patients without a definitive diagnosis have symptoms that are amenable to treatment, if the appropriate diagnosis is made. Secondly, untreated symptoms reduce productivity due to both presenteeism and absenteeism; proper treatment can improve the economic burden of this highly prevalent disorder. Thirdly, patients with symptoms of IBS have inappropriate fears and concerns about their symptoms and this may lead to unnecessary testing. Fourthly, lack of a diagnosis may lead to unnecessary procedures and surgeries; in fact, patients with IBS are much more likely to undergo cholecystectomy, appendectomy, and hysterectomy than matched controls.4

Why making a diagnosis of IBS is so difficult

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

The diagnosis of IBS is difficult because symptoms are non-specific and there is no biological marker to accurately detect and diagnose IBS. We are all intimately familiar with a host of other conditions with symptoms that can mimic IBS [e.g., inflammatory bowel diseases (IBD), celiac disease, lactose intolerance, microscopic colitis]. Nevertheless, when diagnostic criteria are fulfilled, and alarm features are absent, the need for diagnostic tests should be minimal. This concept is important to address on a global basis because it is physically, and economically, impossible to perform diagnostic testing, no matter how limited, in all patients with IBS symptoms; this is especially true in developing countries and primary care centers. Requiring that each patient with IBS symptoms perform a battery of laboratory tests (complete blood count, thyroid hormone levels, celiac disease antibodies), followed by upper endoscopy with duodenal biopsies, colonoscopy with random biopsies, lactose and fructose breath tests, and a CT scan of the abdomen and pelvis will assure the physician that this patient with abdominal pain and diarrhea does not have hyperthyroidism, celiac disease, lactose or fructose malabsorption, IBD, microscopic colitis, or colon and pancreatic cancer. However, in the vast majority of cases this is unnecessary, extremely expensive, and intrusive and risky for the patient. And, even with extensive testing, there is always the very small possibility that an organic disorder will be missed. That thought is what drives many physicians to routinely order a battery of expensive diagnostic tests, although the yield is exceedingly low in the general IBS population. Routine follow-up visits with targeted diagnostic studies for the persistently symptomatic patient are a more cost-effective approach that is also more reassuring to the patient.

The Rome criteria, including Rome III, encourage clinicians to make a positive diagnosis on the basis of symptoms and emphasize that IBS is not a diagnosis of exclusion despite its broad differential diagnosis. The Rome III committee points out that “IBS is often properly diagnosed without testing.”5 However, critics have noted that these criteria were developed by consensus, appear unable to discriminate IBS from other chronic intestinal diseases, and have not been subjected to validation in prospective studies.6–8 Nevertheless, this might be considered as misinterpreting the concept of validation by saying that because no validation studies for Rome III have been done, then Rome III is not valid; in fact one could interpret the other way, that professionals are so sold on the criteria that they do not choose to do it. Finally, and most importantly, physicians routinely ignore published criteria and most still believe IBS is an exclusion diagnosis and not a positive diagnosis.

In 2010, a survey showed that only 8% of experts endorsed IBS as a diagnosis of exclusion whereas 72% of community providers shared this belief.9 In fact, frontline providers were especially prone to order a wide variety of tests with low diagnostic yield. At this point we have to emphasize that when deciding to order a diagnostic test, clinicians need to consider the pre-test probability of the disease in question, based on the prevalence of the disease in patients with specific symptoms.

Many clinicians are concerned about overlooking alternative diagnoses and believe that performing a battery of tests is a form of defense against litigation. However, as stated by Spiegel et al.9 clearly this is a suboptimal reason to pursue diagnostic testing for any reason, and there are data that indicate that the quality of the physician–patient relationship is a critical predictor of outcomes, and a more important predictor of litigation than testing proclivity.10 In addition, a negative diagnostic test is not useful in allaying patient fears or concerns as demonstrated by a study showing that a negative colonoscopy is not associated with reassurance or improved quality of life in young IBS patients.11

An especially interesting observation is that among providers willing to proactively diagnose IBS on the basis of history and physical examination alone, less than half are willing to inform the patient of their belief until additional testing has nonetheless been performed.9 Thus, the diagnosis of IBS is frequently thought of by the physician, occasionally transmitted to the patient, and rarely written in a prescription.

Diagnostic criteria for IBS: from Manning to many

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

In 2009, the American College of Gastroenterology Task Force conducted an outstanding systematic review of the accuracy of symptom-based criteria in the diagnosis of IBS.12 Individual analysis of symptoms such as abdominal pain, loose or frequent stools associated with pain, incomplete evacuation, mucus per rectum, and abdominal distention all had poor accuracy in IBS diagnosis. The one with the highest sensitivity (90%) was lower abdominal pain but specificity was very poor (32%); however, this good sensitivity is obviously explained by the fact that abdominal pain is part of the IBS definition. It is worth mentioning that visible abdominal distention, a sign not included as a key criterion for IBS diagnosis, had the highest specificity (77%), although sensitivity was low (39%).12 A year before another excellent review analyzed whether the history and physical examination helps to establish that IBS is the cause of a patient’s lower gastrointestinal tract symptoms;13 again, individual symptoms were of not much help (Fig. 1).

image

Figure 1.  Sensitivity, specificity, and positive and negative likelihood ratios of individual symptoms for the diagnosis of irritable bowel syndrome. Modified and created with data obtained from table 3 in the paper published by Ford et al.13

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The poor sensitivity and specificity of individual symptoms to diagnose IBS led to the development of several sets of diagnostic criteria (Fig. 2).5,14–17 The first attempt was published in 1978 by Manning et al.14 The so-called Manning criteria have lasted more than 30 years and have been very useful. Astonishingly, these criteria were developed using data from only 32 patients with IBS and 33 patients with organic disease. It was found that four symptoms were significantly more common in IBS patients and that when another two symptoms were added, the discriminative capacity between the two groups increased further. Several surveys were later done to confirm the usefulness of the Manning criteria to discriminate IBS from organic disorders but many of them were hampered by the large proportion of patients with upper gastrointestinal diseases that, of course, are in most cases out of the clinical differential diagnosis. Thus, in one study, the four independently significant Manning symptoms were able to discriminate IBS from peptic ulcer disease but only abdominal distention distinguished IBS from IBD.18 Nevertheless, the Manning criteria have been the most extensively studied and, as reported by Dang et al. in this journal issue,6 when two of four main symptoms were used a sensitivity of 91% and specificity of 70% was established; when two of six symptoms were used, the sensitivity ranged from 84% to 94% and the specificity was 55%; finally when ≥3 of six symptoms were used, the sensitivity ranged from 63% to 90% and the specificity ranged from 70% to 93%.

image

Figure 2.  Diagnostic criteria used to define irritable bowel syndrome (IBS).

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In 1984, Kruis et al.15 reported that the combination of several symptoms for more than 2 years, in the absence of alarm symptoms and some simple blood test results, helped to make the diagnosis of IBS. They used a scoring system to identify IBS patients by assigning positive points to functional symptoms and negative points to “red flag” symptoms. Thus, a score of ≥44 was reported to have a sensitivity of 64% and specificity of 99%. However, another study used the same cut-off score and found a sensitivity of only 47%.19

The Rome criteria, with their three different consecutive versions over 15 years (Rome I, II, and III), have been all heavily promoted. Although no longer used, it is worth mentioning that one study reported that the sensitivity and specificity of the Rome I criteria were 65% and 100%, respectively, although this study included the absence of red flags.20 Another study reported a sensitivity of 85% and specificity of 71%.21 The overall sensitivity of Rome I criteria for the diagnosis of IBS is 65–85% while the specificity is 70–100%.6

In 1999, the criteria were revised and the Rome II criteria published.17 This iteration required that at least two of three criteria relating abdominal pain to bowel symptoms had to be present. Similar to Rome I, Rome II required that symptoms had to be present for at least 12 weeks. The main difference was that these weeks did not have to be consecutive but rather throughout a 1-year period. Irritable bowel syndrome diagnostic sensitivity using Rome II criteria ranged from 64% to 89% and specificity from 66% to 73%.6 After the Rome II criteria were published, many clinicians and researchers thought that they were too restrictive and too focused on clinical trials, and did not represent the typical IBS patient seen in clinical practice.22–24 This led to the development of the Rome III criteria.5

More recently, a study used variation in stool consistency and frequency as a means of diagnosing IBS with diarrhea.25 The authors coined the term “irregularly irregular” as a characteristic of IBS and found that it performed better than the Rome criteria in discriminating active IBD from IBS. However, it is important to emphasize that the Los Angeles/IBS criteria differentiate only IBS with diarrhea from other gastrointestinal conditions causing diarrhea. The authors used ≥3 stool forms (irregularly irregular bowel form and frequency) per week as a method of discriminating IBS from non-IBS and reported a sensitivity of 81% and specificity of 60%. Although intriguing, this study has not been replicated and does not address patients with IBS and constipation and IBS with mixed or alternating symptoms of constipation and diarrhea.

At this point it has to be highlighted that, in spite of all their possible deficiencies, Rome criteria are currently the only ones accepted by regulatory agencies (including FDA), pharmaceutical companies, and most academic investigators.

Detecting alarm features to suspect other diseases mimicking IBS

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

The classic gastrointestinal alarm features include rectal bleeding, unintentional weight loss, anemia and nocturnal symptoms, as well as a family history of colorectal cancer, IBD, or celiac disease. The main concern of most physicians when facing a patient with IBS-type symptoms is missing colorectal cancer. A systematic review of the literature analyzed the utility of alarm features in almost 20 000 patients presenting with lower gastrointestinal symptoms.26 The main findings of this review were that the presence of abdominal pain reduces the likelihood of having colorectal cancer, and the absence of pain increases it. The presence of rectal bleeding had a sensitivity of 64% and a specificity of 52%. The utility of the presence of anemia for diagnosing colorectal cancer in patients with lower digestive symptoms was also evaluated and the authors reported a sensitivity of 19% and specificity of 90%. Similar data were obtained for weight loss with a sensitivity of 22% and specificity of 89%. Regarding the utility of nocturnal symptoms to discriminate patients with organic disorders from functional disorders, studies suggest that nocturnal abdominal pain is no more likely in organic diseases than it is in IBS.26 Therefore, the accuracy of so-called “alarm features” to uncover organic diseases in patients with symptoms of IBS is disappointing. Nevertheless, many well-recognized guidelines still recommend the evaluation for alarm features, as demonstrated by the AGG Task Force recommendations which state “in patients who fulfil symptom-based criteria, the absence of selected alarm features, including anemia, weight loss, and a family history of colorectal cancer, IBD or celiac disease, should reassure the clinician that the diagnosis of IBS is correct.”12

Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

The clinician has a battery of widely available diagnostic tests that can be ordered to exclude organic disease in patients with IBS symptoms. The assumption is that normal diagnostic tests will reassure the patient that there is “nothing important” and the diagnosis of IBS is correct. However, the truth is that, in most cases, this is more important for the clinician than for the patient.

A number of different reviews have all concluded that the prevalence rates of Crohn’s disease, ulcerative colitis, colorectal cancer, and thyroid disease are not significantly different in patients with IBS symptoms compared with the general population;12,26 however, lactose intolerance seems to be more prevalent.12 Although still widely debated, a recent study reported that the prevalence of celiac disease was no different in non-constipated IBS patients compared with healthy controls.27 In contrast, the systematic review performed by the ACG Task Force identified seven case–control studies including 2978 individuals (1052 with IBS), which used serum antibodies (anti-endomysial or tissue-transglutaminase) to screen for celiac disease: 3% of the IBS patients vs 0.7% of controls had positive results; small bowel biopsies evidenced celiac disease in 3.6%vs 0.7%, respectively.12 Decision analytic models have demonstrated the cost-effectiveness of serologic screening for celiac disease as long as the prevalence exceeded 1%.28 Based on these findings, routine serological screening for celiac disease in patients with IBS (mainly with diarrhea) is recommended.

Lactose maldigestion is demonstrated by lactose breath testing in about 38% of subjects with IBS symptoms and 26% of controls.12 Nevertheless, it is difficult to prove causation between lactose maldigestion and IBS symptoms. Other carbohydrates such as fructose and sucrose can also cause or exacerbate IBS symptoms; this has to be analyzed individually according to the presence of individual predominant symptoms, mainly diarrhea and bloating or abdominal distention.29

Clinicians frequently order complete blood count and serum chemistries but the likelihood of uncovering important organic diseases is low. Nevertheless, these tests are included in some well-developed IBS diagnostic algorithms (based on the analysis of the literature, combined with consensus of experienced clinicians)30 and also ordered as part of the “annual check-up” to almost “everyone” attending a clinician; therefore, it might be argued that there is no reason not to do it in patients with IBS symptoms just because IBS is suspected. Finally, stool examination for ova and parasite is of little value in developed countries, and the utility of abdominal imaging tests in patients with suspected IBS and no alarm features is scarce.12

The topic of small intestinal bacterial overgrowth (SIBO) has focused much attention on IBS pathogenesis and treatment during the last decade. However, despite extensive publicity, there is not enough evidence to routinely recommend breath testing for SIBO in patients with IBS and, when suspected, it might be more cost-effective to initiate a therapeutic trial with non-absorbable antibiotics.31

Colonic imaging in an IBS patient with no alarm features is unlikely to reveal structural disease that might explain the patient’s symptoms. Therefore, it is recommended that any patient older than 50 years of age should undergo colonic imaging for the purpose of colorectal cancer screening. Patients younger than 50 years without alarm features need not undergo colonic imaging. Patients with IBS symptoms and alarm features should undergo colonic imaging to exclude organic disease.12 In patients with diarrhea or alternating bowel movements, when performing colonoscopy, the terminal ileum should be carefully inspected and colonic biopsies should be done to exclude IBD and microscopic colitis, respectively.

Looking for biomarkers in IBS

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

Biomarkers have been defined as a characteristic that is measured and evaluated as an indicator of normal biological processes, pathogenetic processes, or pharmacologic responses to a therapeutic agent.32 As explained by Mayer in an excellent editorial,33 an implicit assumption is the specificity of a particular biomarker for a specific disease or disorder. Over the last few decades there has been a great interest in the development of biomarkers in organic disorders trying to improve diagnostic accuracy and accelerate drug development. This has also been attempted in functional digestive disorders, such as IBS and functional dyspepsia, although it is highly unlikely that the identification of a single biomarker would be able to completely explain the diverse and heterogeneous symptom expression in these highly prevalent syndromes.33 Nevertheless, Camilleri34 summarized the evidence supporting the utility of noninvasive colonic transit measurements for drug development for colonic motility disorders.

There has also been a surge in the identification and validation of endophenotypes. The endophenotype concept has arisen in the field of psychiatry in an attempt to find latent phenotypic constructs that are intermediate between the complex clinical symptom presentation and genes.33,35 Just to summarize the state of the art in this area let us transcribe what Emeran E. Mayer stated in his editorial: “It would seem that no matter how exciting and promising the new approaches are, until reliable biomarkers, reproducible endophenotypes, and related networks have been identified and validated, the field of neurogastroenterology will have to live for some time with the traditional symptom based approach to drug development.”33

Some studies have tried to differentiate IBS from organic intestinal disease using inflammation biomarkers. Tibble et al.21 assessed the utility of fecal calprotectin (Cal), small intestinal permeability, Rome I criteria, and laboratory markers of inflammation [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)] in distinguishing organic from non-organic intestinal disease. The sensitivity and specificity of Cal for organic disease were 89% and 79%, respectively, and that of intestinal permeability for small intestinal disease were 63% and 87%, respectively. An abnormal Cal test had an OR for organic disease of 27.8 (95% CI, 17.6–43.7) compared with 4.2 (95% CI, 2.9–6.1; P < 0.0001) and 3.2 (95% CI, 2.2–4.6; P < 0.0001) for elevated CRP and ESR.

In a different study fecal lactoferrin (Lf), Cal, polymorphonuclear neutrophil elastase (PMN-e), and CRP values were compared in patients with IBD and IBS.36 Ulcerative colitis or Crohn’s disease patients with active inflammation showed significantly higher levels of Lf, Cal, and PMN-e in feces as well as serum-CRP when compared to patients with inactive inflammation as well as patients with IBS. The overall diagnostic accuracy in IBD patients was 80% for Lf, 80% for Cal, 74% for PMN-e, and 64% for CRP. Another study investigating the utility of fecal Lf as a marker of inflammation also found significantly higher levels in IBD patients compared with IBS/healthy controls.37 The sensitivity, specificity, positive, and negative predictive values of Lf in distinguishing active IBD from IBS/healthy controls were 67%, 96%, 87%, and 87%, respectively.

The combination of several biomarkers did not increase the utility of individual biomarkers. The sensitivity and specificity of the 10-biomarker algorithm for differentiating IBS from non-IBS were 50% and 88%, respectively; the positive predictive value was 81%, and the negative predictive value was 64% at 50% IBS prevalence in the validation cohort; the overall accuracy was 70%.38

As recently published by Sperber and Drossman,39 physiologically based assessment can complement symptom-based diagnosis but does not replace it. Thus, while biomedical investigations may be of value in explaining the basic mechanisms of “disease,” they do not explain “illness.” Biomarkers (as they become available) and other physiological descriptors can be integrated into a multidimensional profile of IBS patients to better tailor treatment to each individual patient. This integrated profile will include clinical, psychological, and physiological descriptors that will define subsets of patients and guide treatment.39

Some key questions when thinking about the diagnosis of IBS

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

What are the typical clinical manifestations in IBS?

The Manning criteria included the following symptoms as part of IBS: abdominal pain relieved by defecation, more frequent stools with onset of pain, looser stools with onset of pain, mucus per rectum, feeling of incomplete emptying, and visible abdominal distention. The Rome I criteria required the presence of abdominal pain and Rome II limited it to the pain-related symptoms that had clustered in factor analyses. Four of the Manning symptoms co-varied (bloating loaded only weakly) in women,40 and three of them (excluding bloating) co-varied. In a similar study conducted in students, clustering of three of the primary symptoms (excluding bloating) occurred in females, whites, and blacks, while clustering of all four symptoms occurred in males (bloating loaded weakly).41 The three Rome II core symptoms clustered together similarly in US gastroenterology patients and Italian gastroenterology patients’ relatives.42 In addition, similar clustering of symptoms occurred in the US, Australian, German, and Swedish community surveys.43 Therefore, the symptoms that were included in the Rome III criteria were abdominal discomfort or pain relieved by defecation, associated with a change in frequency of stool, or associated with a change in stool form.

The pain-related criteria were unchanged, a decision supported by factor analyses in non-patients40,41 and their equal presence in female and male patients.44“Distention” was not included as an obligatory symptom considering that it was less consistently present and less commonly experienced in males than in females.45,46 Bloating or feeling of abdominal distention was included as one of the symptoms that cumulatively support the diagnosis of IBS. However, some studies have suggested that bloating is one of the most bothersome symptoms in IBS, even as important as pain.46,47 Thus, the symptoms of bloating or a feeling of abdominal distention should once again be evaluated and considered for inclusion when the IBS diagnostic criteria are revised.

The temporal relationship between abdominal discomfort/pain and bowel movements is another aspect to be reconsidered. As an example, one of the three features required by Rome III to fulfill the diagnosis of IBS is the presence of “abdominal discomfort or pain relieved by defecation,” although a considerable number of patients are not very much improved after defecation, and in some cases, the pain worsens. More clinical data and symptoms analysis in this field are required.

Is IBS different from functional chronic constipation and from functional chronic diarrhea?

According to Rome III criteria, IBS patients are grouped into different subtypes based on the predominant stool consistency: IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), IBS mixed type (IBS-M), and IBS unsubtyped (IBS-U).5 By definition, all IBS subjects, including IBS-C patients, need to have abdominal pain or discomfort to make the diagnosis whereas in functional chronic constipation abdominal pain/discomfort is supposed to be absent. However, accurately discriminating these two disorders is not always easy; both share symptoms such as bloating (difficult to differentiate from discomfort), IBS-C patients may complain of only mild pain/discomfort, and functional (often referred to as chronic) constipation (CC) patients sometimes have “some” pain/discomfort. Moreover, the same treatments (including new laxatives and prokinetics) have been used for both conditions with successful results.48–54 In fact, there is a group of patients with constipation who have abdominal pain/discomfort but who do not fulfill the diagnostic criteria for IBS.

Therefore, rather than being separate diagnoses, the authors proposed that they are actually part of the same condition, anchored on different ends of the spectrum of severity.

Another way to classify functional bowel disorders might be to consider the complex relationship between abdominal pain and disordered defecation, with an emphasis on thinking of these disorders as part of a broad spectrum, rather than as completely distinct disorders. This approach is illustrated in Fig. 3.

image

Figure 3.  Irritable bowel syndrome (IBS), functional chronic constipation (CC), functional chronic diarrhea (CD) and bloating might be conceptually considered in different ways: (A) as individual conditions that need independent diagnosis; (B) as individual conditions that, in clinical practice, frequently overlap; and (C) as part of a broad spectrum with differences in the presence/severity of different clinical manifestations.

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Some studies, using cluster analysis, have concluded that CC and IBS are two distinct disorders while other investigators believe that both disorders represent different ends of the same broad spectrum.55,56 Wong et al.56 concluded that the overlap in symptoms between IBS-C and functional constipation, and the tendency to alternate between these two diagnoses suggest that the Rome III criteria may not be able to identify etiologically distinct groups of patients, and that these two conditions are quantitatively different (with IBS-C being more severe) but qualitatively similar.

Similarly, functional chronic diarrhea (or watery diarrhea without – or with minor – abdominal pain) may have some overlap with IBS-D. Although not well studied, perhaps depending on the type and severity of diarrhea in a patient meeting IBS criteria, the diagnostic approach should be different. For example, consider the case of patients with watery diarrhea having some degree of abdominal discomfort/pain; the need for diagnostic test is this specific group is supported by studies demonstrating that in patients with chronic watery diarrhea (>3 loose or liquid bowel movements a day for at least 4 weeks and a stool weight >200 g day−1) bile acid malabsorption is the cause in 45% of cases, while sugar malabsorption (16%), gluten-sensitive enteropathy (16%), and both bile acid and sugar malabsorption (3%) were other causes; only 19% of the patients remained without a specific diagnosis.57

Another important diagnosis not to miss in IBS-D type patients is microscopic colitis. Limsui et al.58 evaluated 131 cases of microscopic colitis and found that 53% and 56% met Rome I and Rome II criteria for IBS, respectively; in fact one-third of them had previously been diagnosed with IBS.

Sometimes two patients with the same diagnosis of IBS have nothing (or almost nothing) in common: for example, one having constipation and the other diarrhea. In many cases the diagnosis of IBS is much closer to that of functional chronic constipation or functional chronic diarrhea that to itself. Fig. 4 shows different models to explain the clinical relationship among abdominal pain/discomfort and bowel movement abnormalities in functional bowel disorders.

image

Figure 4.  Different models to explain the clinical relationship among abdominal pain/discomfort and bowel movements abnormalities in functional bowel disorders: (A) Current and classical model where the presence of abdominal pain or discomfort is mandatory to make the diagnosis of irritable bowel syndrome (IBS) and subtyped according to the association of constipation or diarrhea; (B) Consider bowel movement abnormalities as the main clinical manifestations and subdividing functional chronic constipation (CC) as well as functional chronic diarrhea (CD) according to the presence or absence of abdominal pain/discomfort; in this case IBS should be considered only in the presence of bowel irregularity.

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Should psychological aspects be included as part of the IBS diagnostic criteria?

Rome III stated that IBS is better understood using the biopsychosocial model, which emphasizes the importance of biologic and psychosocial factors. However, psychological aspects are not included in the current Rome criteria when trying to distinguish patients with functional vs organic causes. Little data are available to guide us through the complex question of whether using these co-factors will improve our ability to diagnose IBS. This area of research is incredibly complicated, in part due to the large number of psychological factors that need to be evaluated, the fact that psychological disorders are frequently not reported by either patients or clinicians, and because the rates of different psychological disorders vary greatly in the community compared to primary care providers compared to tertiary care specialists.

In summary, the evaluation and diagnosis of IBS remains confusing and complicated for clinicians. Reasons for this are many, but include the fact that the Rome III criteria remain under-recognized and underused; the diagnosis remains one of exclusion with excessive testing performed; and confusion about overlapping disorders has blurred the clinical borders that distinguish IBS. Although these points may engender despair in many providers, clinicians should not give up hope on the diagnosis and treatment of IBS. Although not perfect (and no diagnostic criteria are), the Rome III criteria can be used to make a presumptive diagnosis and allow the initiation of therapy based on the predominant symptom.

That is an optimistic view of the field that may not sit well with some critics. A less optimistic view is presented in the current issue of Neurogastroenterology and Motility, in which the Rome diagnostic criteria, specifically Rome III, are profoundly and fairly criticized.6 A systematic review shows poor validity and utilization of Rome III and demonstrates that the Manning criteria are more accurate. At the end of the paper the authors ask if there is a need for Rome IV if Rome III were not successful. In our opinion the answer is clearly YES. In the ideal world, the Rome III criteria would have been widely accepted by all practitioners and would have proved to increase the ease and accuracy of diagnosing IBS. Unfortunately this did not turn out to be true, which is why there is a need for the Rome IV project. There is no other way to improve things than trying again with renewed strengths. Hopefully, Rome IV will be able to fulfill researcher and clinicians expectations, but – more importantly – patient’s needs.

Disclosure

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References

FM has acted as an advisor to Almirall, Menarini, Novartis, Shire-Movetis, and has undertaken speaking engagements for Abbott, Alfa Wasserman, Almirall, Janssen, Menarini, Novartis, and Shire-Movetis. BL has served on the following scientific advisory boards over the past 2 years: Givens, Ironwood, Ono, Prometheus, and Takeda.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Why making a diagnosis of IBS is so important
  5. Why making a diagnosis of IBS is so difficult
  6. Diagnostic criteria for IBS: from Manning to many
  7. Detecting alarm features to suspect other diseases mimicking IBS
  8. Diagnostic tests to exclude other diseases: reassurance for the patient or the physician?
  9. Looking for biomarkers in IBS
  10. Some key questions when thinking about the diagnosis of IBS
  11. Disclosure
  12. Author contribution
  13. References
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