What Is New in Rome IV
Laboratorio de Hígado, Páncreas y Motilidad (HIPAM), Unidad de Investigación en Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México (UNAM), Hospital General de México, Dr. Eduardo Liceaga, Mexico City, Mexico
Center for Functional GI and Motility Disorders at University of North Carolina, NC, USA
Center for Education and Practice of Biopsychosocial Care and Drossman Gastroenterology, Chapel Hill, NC, USA
Abstract
Functional gastrointestinal disorders (FGIDs) are diagnosed and classified using the Rome criteria; the criteria may change over time as new scientific data emerge. The Rome IV was released in May 2016. The aim is to review the main changes in Rome IV. FGIDs are now called disorders of gut-brain interaction (DGBI). Rome IV has a multicultural rather than a Western-culture focus. There are new chapters including multicultural, age-gender-women’s health, intestinal microenvironment, biopsychosocial, and centrally mediated disorders. New disorders have been included although not truly FGIDs, but fit the new definition of DGBI including opioid-induced gastrointestinal hyperalgesia, opioid-induced constipation, and cannabinoid hyperemesis. Also, new FGIDs based on available evidence including reflux hypersensitivity and centrally mediated abdominal pain syndrome. Using a normative survey to determine the frequency of normal bowel symptoms in the general population changes in the time frame for diagnosis were introduced. For irritable bowel syndrome (IBS) only pain is required and discomfort was eliminated because it is non-specific, having different meanings in different languages. Pain is now related to bowel movements rather than just improving with bowel movements (ie, can get worse with bowel movement). Functional bowel disorders (functional diarrhea, functional constipation, IBS with predominant diarrhea [IBS-D], IBS with predominant constipation [IBS-C], and IBS with mixed bowel habits) are considered to be on a continuum rather than as independent entities. Clinical applications such as diagnostic algorithms and the Multidimensional Clinical Profile have been updated. The new Rome IV iteration is evidence-based, multicultural oriented and with clinical applications. As new evidence become available, future updates are expected.
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Keywords: Constipation, Diarrhea, Functional gastrointestinal disorders, Irritable bowel syndrome, Rome IV
Article notes
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Received 2016 Dec 13; Accepted 2017 Jan 2; Issue date 2017 Apr.
Introduction
Functional gastrointestinal disorders (FGIDs) classification and diagnostic criteria began in the late 1980s, when a group of international experts were recruited by Professor Aldo Torsoli from Italy to develop Working Teams for the International Gastroenterology meeting in Rome 1988. The purpose was to answer difficult questions using a consensus methodology through the Delphi approach about a group of gastrointestinal disorders that had little scientific-based evidence to understand etiology pathophysiology and treatment at the time. One committee was established to develop for the first time diagnostic guidelines for irritable bowel syndrome (IBS). This was chaired by Prof W Grant Thompson from Canada and published in 1989.1,2 This IBS Working Team was the starting point for the Rome process that later generated consensus-based criteria for other disorders without an anatomical or structural basis. With the support of Dr Enrico Corazziari representing Dr Aldo Torsoli, Dr Douglas A Drossman, a member of the original IBS Working Team, set up another working team to create a classification system with diagnostic criteria for all of the FGIDs. The classification was divided into 5 anatomical regions including the esophagus, gastroduodenal tract, bowel, biliary tract, and anorectal area, and was published in Gastroenterology International.3 A refinement of the classification system was made with a series of papers in the same journal by 5 additional working teams.3–7 In all, there were criteria for 21 FGIDs and this led to the development of a research instrument to conduct an epidemiological survey used for the first US Householder Epidemiological Study,8 a seminal paper in the field. These papers were further compiled in a book entitled “The functional gastrointestinal disorders: diagnosis, pathophysiology and treatment,” published in 1994.9
The birth of the Rome process and its classification system served as the basis for an incredible explosion of research in the field as well as to legitimize the patient’s having these symptoms.10 However, with evolving science and new evidence, the Rome process became a dynamic one requiring updates leading to revisions in the publications. Therefore, 28 years after the first Working Team on IBS, and 10 years after the last iteration of the Rome process (Rome III) were published, the Rome IV process and consequently the modified Rome IV classification and criteria have been published in a supplement of Gastroenterology as well as in a collection of books, both in hard copies and online, this past May 2016.11,12
This was accomplished by a rigorous process of prospective and retrospective data collection, synthesis, data discussion, group decision making, and peer-review.13 Table 1 summarizes the Rome IV process.
| Years | Level | Actions |
|---|---|---|
| 2008 | Rome Foundation Board of Directors | Identified key areas to acquire preliminary knowledge for the Rome IV Chapter Committeest |
| 2010–2012 | Rome Foundation Board of Directors | Creation of the Rome IV Editorial Board Members |
| Rome IV Editorial Board Members | Identified Chairs and Co-chairs of the 18 committees | |
| Rome IV Committees Chairs and Co-chairs | Selection of committee members to produce Rome IV Chapters | |
| Rome Foundation Board of Directors | Creation of Support Committees to provide ancillary service to the chapter committees | |
| 2013 (May) | Rome Foundation Board of Directors | Orientation meeting |
| Support Committees | Presented their work | |
| 2013–2015 | Rome IV Committees | Critically synthesized the literature and created the requested documents through several revisions. |
| 2014 (December) | Rome IV Committees | Meeting in Rome (Rome IV Conference) to revise the documents and established consensus on scientific content an diagnostic criteria |
| Rome IV Editorial Board, Committee Chairs and Co-Chairs | Harmonization meeting to summarize and present their committees' recommendation to the group | |
| 2015 | Committee Chairs and Co-Chairs | Each document was sent out for peer-review by international experts |
| 2015 (Autumn) | Committee Chairs and Co-Chairs and Members | Manuscripts for the Rome IV Gastroenterology supplements were created |
| Rome IV Editorial Board | Reviewed the manuscripts for the Rome IV Gastroenterology supplements | |
| Rome IV Committee Members | Signed off on all documents before they were sent to copy editor for final check |
Rationale for a Symptom-based Classification
A FGID (eg, functional heartburn and IBS) relates to the patients’ interpretation and reporting of the illness experience, and it is classified primarily in terms of symptoms. A symptom is an experience perceived as different from normal, while a syndrome (eg, any of the FGID) is a consistent association of symptoms.13 While a FGID may have an abnormal motility finding such as rapid intestinal transit in IBS patients with diarrhea (IBS-D)14 or a pathologic finding such as increased in colonic mucosal mast cells,15 these factors are neither sufficient nor necessary for defining a FGID. Thus, by moving from motility based categorization to a symptom based method we can identify underlying pathophysiological determinants, be they motility, hypersensitivity, or brain-gut dysfunction. This classification based on symptom groupings (developed by population cluster analysis and clinical studies) thus represent what patients bring to doctors. This approach opens the door for the study of additional pathophysiological processes. It is not coincidence that the growth in the work on visceral hypersensitivity and sensitization, brain-gut interactions, microbiota etc, began right at the time of the classification system published in 1990.16–19 Because patients were selected for these studies based on symptom criteria which defined the cohorts. Other benefits include the ability of having homogeneous groups for clinical trials with the Food and Drug Administration (FDA) and European Medicines Agency endorsement of these criteria. This led to a marked increase in drug discovery and use.20–22 Finally such a classification system provides legitimization for patients and doctors.
A New Definition for Functional Gastrointestinal Disorders: Disorders of Gut-Brain Interaction
Although the word functional has been embedded in our terminology, there has been a longstanding discussion to eliminate this term because of the term being non-specific and potentially stigmatizing. Based on more recent scientific knowledge that proposes the interaction of multifactorial pathophysiological factors involved on the generation of these disorders, a revised definition was created: disorders of gut-brain interaction (DGBI) to help clarify its meaning. These disorders are defined as a group of disorders classified by GI symptoms related to any combination of motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, and/or central nervous system processing. We will be using this new term throughout the article to represent FGIDs.
Functional has been removed from the chapters and article titles (for example Gastroduodenal Disorders instead of Functional Gastroduodenal Disorders) and from certain diagnoses when possible (for example Fecal Incontinence instead of Functional Fecal Incontinence). The Rome Foundation understands that it will take time until the term functional is completely eliminated from the health care language, and in some clinical disorders the term functional was retained to distinguish them from other similar disorders (for example Functional Diarrhea) until a more appropriate term can be used.13
Multicultural Orientation
Traditionally, the Rome approach was based on Western knowledge to understand patients’ symptoms, which has limitations for other countries and cultures.2,13 Thus, one of the major changes in Rome IV is addressing these limitations by moving from a Western ethnocentric focus to a multi-cultural orientation. This could be uniquely accomplished through 117 experts from 23 countries as part of the Rome IV process. What resulted was the inclusion of a new chapter devoted entirely to multi-cultural information that addresses the global perspective on these disorders. This chapter, “Multi-cultural Aspects in Functional Gastrointestinal Disorders (FGIDs)”23 was an extension of the Rome Foundation Working Team on Multinational, Cross-Cultural Research, which completed its work in 2014.24–26 The chapter elaborated on a conceptual model relating to the interaction between culture and DGBI, focusing on patients, physicians, food and eating, and culture in symptom interpretation and clinical manifestations.27 Culture defined as the values, beliefs, norms, and practices of a particular group that are learned and shared28 can guide, thinking (eg, food taboos), decisions (eg, illness explanatory model), and actions (eg, treatment choice). Patients have symptoms or disease related beliefs that affect their concerns, anxieties, and expectations of the health care process known as explanatory models.29 Although factors such as the cultural background, educational level, and sex can contribute to these explanatory models, we also recognize that local biologics including genetics, microbiome/post-infectious IBS, environmental hygiene, cytokines, and the effects of CNS, can impact on symptom generation, manifestation, and interpretation. Also considered were the explanatory models of illness that may impose a barrier to the physician-patient relationship; gender; family relationships that can have a significant effect on the illness experience of the patient; and last but not least, symptom reporting as this varies between groups.23,30 The most characteristic issue in terms of symptom reporting is bloating, a term confined primarily to the English language but absent in Spanish or Italian.23 Also, the differentiation of bloating from postprandial fullness imposes a linguistic and cultural issue. For example, in China, postprandial fullness is limited to the epigastrium while bloating refers to a sensation of gas that is present in most, if not the entirely all over the abdomen and can reflect abdominal discomfort. However, discomfort is another expression without a translation to many languages. Therefore, pictograms may have to be designed and validated in the future for conducting cross-cultural research.23,27
As for food, in most cultures it plays a prominent role in DGBI patient symptom attribution and reporting and cultural factors can have a negative or positive meaning to food such as nocebo or placebo properties. Finally, physicians need to be prepared to work in a multicultural milieu to address this issues and be aware of how can religion and culture can affect treatment modalities including Complementary and Alternative Medicine, which should be included in the Western type of treatments. Notwithstanding, the differences in healthcare systems can influence the diagnostic work-up and treatment itself.27
New Chapters
Not only the previous Rome III chapter on “Gender, age, society, culture, and the patients perspective” was split to give rise to 2 new Rome IV chapters, the “Multicultural Aspects in Functional Gastrointestinal Disorders”23 and “The Age, Gender, and Women’s Health,”31 and also a new chapter entitled “The Intestinal Microenvironment and Functional Gastrointestinal Disorders,”32 was added based on the increasing evidence supporting a role for luminal gut factors in the generation of DGBI such as IBS and functional dyspepsia.32 They included the interaction between diet and products of digestions, enteric infections or infestation, the microbe-host interactions including the immune and metabolic responses and biliary acids among others. These factors can interact with the gut mucosa not only triggering a leaky barrier, but in the presence of a permeability abnormality may allow an amplification of signaling from the lumen to neural and immune pathways, generating functional gastrointestinal symptoms.33
The “Psychosocial Aspects of Functional Gastrointestinal Disorders” chapter was changed to “Biopsychosocial Aspects of Functional Gastrointestinal Disorders”34 to reflect the multi-determined nature of these processes. Finally the Rome III chapter on “Functional abdominal pain syndrome,” was changed to “Centrally Mediated Disorders of Gastrointestinal Pain” to reflect the range of gastrointestinal symptoms believed to have a central origin,35 where central dysregulation of pain is the major contributor to the disorder.36 The chapter includes the “Centrally mediated abdominal pain syndrome (CAPS)” resulting from central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability; and a new disorder called narcotic bowel syndrome (NBS) (see “New Disorders” section and “Diagnostic Criteria” section).36
New Disorders
Rome IV has included new diagnoses that have a known etiology, yet they are included because they fit the new definition of DGBI, as related to their effects on altering the function of the CNS or enteric nervous system, and their clinical presentation is similar to DGBI, and the need to be readily recognized by clinicians. Also, they have not been fully accepted as discrete disorders nor have they been well characterized yet.13 These new diagnoses include the NBS (Opioid-Induced Gastrointestinal Hyperalgesia) in the chapter, “Centrally Mediated Disorders of Gastrointestinal Pain”;36 Opioid Induced Constipation in the chapter, “Bowel Disorders”;37 and Cannabinoid Hyperemesis Syndrome in the chapter “Gastroduodenal Disorders.”38
Threshold Changes: Normative Survey
Because there was limited information on the frequency of normal bowel symptoms in the general population, the Rome Foundation conducted a normative symptom study in a non-clinical sample in the USA, to be able to identify the prevalence of normalcy in order to statistically derive abnormal frequencies consistent with DGBI.39 The committee recommended the 90th percentile symptom frequency or men and women as the threshold to define normality.39 For example, the presence of discomfort or pain anywhere in the abdomen was reported in the majority in the general population less than 2–3 days per month to never, and once a week or more for the combined sample occurred in 6.7%. Therefore, the frequency threshold for pain in IBS was set statistically at a minimum of once a week in Rome IV.37,39 Another example is the frequency of pain or burning above the umbilicus, a cardinal symptom for functional dyspepsia depicted in Figure 1. The survey revealed differences in women and men. A threshold of 2–3 days a month was the threshold for women according to the 90th percentile, in contrast to 1 day a month in men. Although the frequency was less common in men than in women, in this case, it was decided to use the thresholds for the combined male and female sample because the differences were small between the 2 of them.40 Furthermore, this higher frequency in women probably responds to an epidemiological phenomenon that explains why many functional gastrointestinal symptoms including uninvestigated dyspepsia are more frequent in women.41,42
Changes in Diagnostic Criteria
The Rome IV categories and diagnoses for DGBI are listed in Table 2.11 In the following section, we describe the changes and new diagnostic criteria that have been included in Rome IV from the upper to the lower digestive tract.
| A. Esophageal disorders | |
|---|---|
| A1. Functional chest pain | A4. Globus |
| A2. Functional heartburn | A5. Functional dysphagia |
| A3. Reflux hypersensitivity | |
| B. Gastroduodenal disorders | |
| B1. Functional dyspepsia | B3. Nausea and vomiting disorders |
| B1a. Postprandial distress syndrome | B3a. Chronic nausea vomiting syndrome |
| B1b. Epigastric pain syndrome | B3b. Cyclic vomiting syndrome |
| B2. Belching disorders | B3c. Cannabinoid hyperemesis syndrome |
| B2a. Excessive supragastric belching | B4. Rumination syndrome |
| B2b. Excessive gastric belching | |
| C. Bowel disorders | |
| C1. Irritable bowel syndrome | C2. Functional constipation |
| IBS with predominant constipation | C3. Functional diarrhea |
| IBS with predominant diarrhea | C4. Functional abdominal bloating/distension |
| IBS with mixed bowel habits | C5. Unspecified functional bowel disorder |
| IBS unclassified | C6. Opioid-induced constipation |
| D. Centrally mediated disorders of gastrointestinal pain | |
| D1. Centrally mediated abdominal pain syndrome | D2. Narcotic bowel syndrome/opioid-induced gastrointestinal hyperalgesia |
| E. Gallbladder and sphincter of Oddi disorders | |
| E1. Biliary pain | E2. Functional pancreatic sphincter of Oddi disorder |
| E1a. Functional gallbladder disorder | |
| E1b. Functional biliary Sphincter of Oddi disorder | |
| F. Anorectal disorders | |
| F1. Fecal incontinence | F3. Functional defecation disorders |
| F2. Functional anorectal pain | F3a. Inadequate defecatory propulsion |
| F2a. Levator ani syndrome | F3b. Dyssynergic defecation |
| F2b. Unspecified functional anorectal pain | |
| F2c. Proctalgia fugax | |
| G. Childhood functional gastrointestinal disorders: neonate/toddler | |
| G1. Infant regurgitation | G5. Functional diarrhea |
| G2. Rumination syndrome | G6. Infant dyschezia |
| G3. Cyclic vomiting syndrome | G7. Functional constipation |
| G4. Infant colic | |
| H. Childhood functional gastrointestinal disorders: child/adolescent | |
| H1. Functional nausea and vomiting disorders | H2. Functional abdominal pain disorders |
| H1a. Cyclic vomiting syndrome | H2a. Functional dyspepsia |
| H1b. Functional nausea and functional vomiting | H2a1. Postprandial distress syndrome |
| H1b1. Functional nausea | H2a2. Epigastric pain syndrome |
| H1b2. Functional vomiting disorders | H2b. Irritable bowel syndrome |
| H1c. Rumination syndrome | H2c. Abdominal migraine |
| H1d. Aerophagia | H2d. Functional abdominal pain - not otherwise specified |
| H3. Functional defecation | |
| H3a. Functional constipation | |
| H3b. Non-retentive fecal incontinence | |
Esophageal Disorders
With Rome III, functional heartburn was associated with no evidence for gastroesophageal reflux.43 However, with the addition of impedance to esophageal pH monitoring it has been shown that 38% patients did not have acid reflux (pH−), yet had a positive symptom association based on the symptom associated probability (SAP+), in other words they had esophageal hypersensitivity with only 29% having true functional heartburn (pH−/SAP−).44 Therefore, a new diagnosis was included, reflux hypersensitivity, defined by the presence of acid sensitivity in the absence of increased acid reflux.45
It must be noted that reflux hypersensitivity can overlap with true gastroesophageal reflux disease that can be identified in patients with known prior pathological reflux or erosive esophagitis in which reflux parameters (number of reflux events and acid exposure) are documented to have normalized on pH-impedance testing on proton pump inhibitors.45
Gastroduodenal Disorders
Functional dyspepsia (FD) remains as an umbrella term referring to patients with postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS).38 In general, PDS is a postprandial syndrome while EPS is not. However, pathophysiological studies investigating the effect of meal ingestion on symptom generation demonstrated that not only postprandial fullness and early satiety but also, epigastric pain or burning and nausea may increase after meal ingestion.46 In other words, they can overlap. Therefore, the definition of PDS acknowledges that besides postprandial fullness and early satiety, patients may perceive epigastric pain and/or burning after meals.38 Also, bloating, belching, and nausea can be present both in PDS and EPS, but vomiting is unusual.
Secondly, in Rome III a diagnosis of FD could be made with no minimum frequency of occurrence required. However, based on the normative survey, Rome IV now require a minimum frequency of occurrence for the dyspeptic symptoms (ie, postprandial fullness, early satiation, epigastric pain, and epigastric burning) before a diagnosis of FD is made (see above in “Normative Survey”) (Fig. 1).
Third, other minor changes included severity identified at least as bothersome (severe enough to impact on daily activities).38 For research purposes, bothersome can be semi-quantitatively defined as ≥ 2 (ie, severe enough to at least distracting from usual activities) in a 5 point-scale to the effect exerted by symptoms on usual activities.
Chronic idiopathic nausea and functional vomiting syndrome were 2 separate entities in Rome III.47 However, because of the lack of evidence to support different diagnostic investigations and treatments for these disorders, and the observation that both symptoms commonly coexist, Rome IV delineated a combined diagnosis called chronic nausea vomiting syndrome.48 Notwithstanding, it was recognized that patients may present only with nausea or vomiting.48
Bowel Disorders
Previous versions of Rome considered functional bowel disorders such as IBS, functional diarrhea, functional constipation, and functional distension (Rome I) as separate entities. Later it was recognized that these disorders could overlap (Rome II–Rome III). However, in the clinic it may be not be possible to confidently separate disorders into separate entities. Such is the case of IBS with predominant constipation (IBS-C) from functional constipation or IBS-D from functional diarrhea. Thus, Rome IV considers that these disorders exist as a continuum rather than as in isolation (Fig. 2).49 Furthermore, it is recognized that bloating and/or distension are common symptoms frequently reported by patients with any functional bowel disorder.49
Irritable bowel syndrome is the most commonly recognized DGBI around the world, notwithstanding is prevalence remains elusive due to the different diagnostic criteria and survey methods used in research studies.50 However, Rome IV has introduced changes in the diagnostic criteria based on the available evidences,51 as well as on the normative survey.39 Firstly, the term discomfort included in the Rome III criteria is now eliminated from the new Rome IV criteria because a previous study showed that asking about discomfort is nonspecific and should be avoided in future Patient reported outcomes. Also, discomfort has different meanings in different languages and is an ambiguous term to patients.51 Thus, only abdominal pain is now included. Based on the Rome normative survey, pain should be present at least 1 day per week during the previous 3 months. As mentioned before, this was supported by the fact that according to the 90th percentile a lower frequency of pain was common in the general population.39,40 In addition, in Rome III, pain or discomfort had to improve with defecation although in many patients, pain increases with defecation or it remains without changes.52 Also, in Rome III, pain or discomfort onset had to be related with the other 2 criteria: onset associated with a changed in frequency of stools; onset associated with a change of form (appearance) of stool.53 Because not in every patient abdominal pain coincided with these changes in stools, onset is now deleted from Rome IV.37 The changes in IBS criteria from Rome III to Rome IV are depicted in Figure 3. It is important to acknowledge that in the first population-based study using Rome IV criteria in English speaking populations, the IBS prevalence decreased by half compared to that with Rome III criteria: 11.1% vs 6.1%, 11.7% vs 5.8%, and 10.6% vs 5.5% in the US, Canada, and the UK, respectively. It is possible that this change is related to the elimination of discomfort from the criteria.54 Also, it is worth mentioning that in other areas like in Asia, patients do differentiate between pain and discomfort and although expressions such as bloating posed difficulty in translatability, bloating is more common than abdominal pain, and patients often report relief of their fullness or bloating with the passage of either stool or flatus.55 Therefore, Rome IV criteria for IBS may need to be adapted in the future for other cultures as the data accumulates using these criteria.
In terms of IBS subtypes, IBS is mainly classified according to the predominant bowel habit for IBS-C, IBS-D, IBS with mixed bowel habits, and unclassified IBS.53 In Rome IV, bowel habits are based on stool forms only during days with abnormal bowel movements (more than one-fourth: 25% of bowel movements).37 This is in contrast to Rome III in which the 25% threshold was determined based on the total number of bowel movements irrespective of whether they were normal or not.53 In fact this led to a predominance of unsubtyped IBS using Rome III as it was the case in several epidemiological studies the USA and Latin America.56–58 The Rome IV IBS subtypes criteria49 are depicted in Table 3.
| IBS Subtype | Criteria |
|---|---|
| IBS-C | More than one-fourth (25%) of bowel movements with Bristol Stool Scale Types 1–2 and less than one-fourth (25%) with Types 6–7. |
| IBS-D | More than one-fourth (25%) of bowel movements with Bristol Stool Scale Types 6–7 and less than one-fourth (25%) with Types 1–2. |
| IBS-M | More than one-fourth (25%) of bowel movements with Bristol Stool Scale Types 1–2 and more than one-fourth (25%) with Types 6–7. |
| IBS-U | Patients meet diagnostic criteria for IBS but their bowel habits cannot be accurately categorized in any of the above subtypes. |
Functional abdominal bloating/distension is diagnosed when either abdominal bloating (subjective) and/or distension (objective/ visible increase in abdominal girth) predominate over other symptoms.49 The addition of distension also reflects the findings with new technologies such as abdominal plethysmography.59 Rome IV recognizes that patients may also report symptoms of mild abdominal pain and/or minor bowel movement abnormalities.
Opioid induced constipation (OIC) is one of the new disorders now included in Rome IV.49 It has a prevalence of 41% in patients with chronic non-cancer pain, and up to 94% of patients taking opioids for cancer-related pain.60
Initial treatment of OIC is similar to that of functional constipation including laxatives and lubiprostone has been approved by FDA for patients with OIC in patients with non-cancer pain.61 Also, opioid receptors antagonists such as naloxone and nalbuphine that are centrally active, can be used but may be related with withdrawal symptoms. Recently, peripherally acting μ-opioid antagonists (PAMORAs) that block the opioid receptors in the gastrointestinal tract but not centrally, have been developed.62
Centrally Mediated Disorders of Gastrointestinal Pain
This category includes 2 disorders, centrally mediated abdominal pain syndrome, formerly in Rome III, functional abdominal pain syndrome, and the new narcotic bowel syndrome/opiate induced hyperalgesia.36
Centrally mediated abdominal pain syndrome can be distinguished from other DGBI by its strong central component and relative independence from motility disturbance or evidence for visceral hypersensitivity. It results from central sensitization with disinhibition of pain signals rather than increased peripheral afferent excitability.36 Symptom related behavior in patients with CAPS that can facilitate their identification include the expression of pain of varying intensity though verbal and nonverbal methods, urgent reporting of intense symptoms, minimizing a potential role for psychosocial contributors, frequently seeking for health care, request for narcotic analgesics, focusing their attention on complete symptom relief, taking limited personal responsibility for self-management, and requesting diagnostic studies.35 CAPS is typically associated with psychiatric comorbidity, but there is no specific profile that can be used for diagnosis, and some degree of gastrointestinal dysfunction may be present.35
The management of CAPS relies on a strong patient-physician relationship, early incorporation of non-pharmacological therapies, and referral behavioral health therapies when needed.63 The later ones can include psychodynamic interpersonal psychotherapy, hypnotherapy, mindfulness, and cognitive behavioral therapy. As for pharmacological therapies, low dose tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors can be used along with the general measurements.36 These medications are initially used for 4–6 weeks and doses can be increased in case of incomplete response for another similar period. If necessary, an augumentation protocol, that is a combination of 2 or more treatments usually at lower dosages, that act at different receptor sites or areas of the brain may be used to enhance the therapeutic effect.64
Narcotic bowel syndrome/opiate induced-gastrointestinal hyperalgesia is characterized by the paradoxical development of, or increases in, abdominal pain associated with continuous or increasing dosages of opioids.65 NBS can occur in patients with DGBI, chronic organic gastrointestinal diseases, and painful malignant or non-malignant diseases.35
Treatment includes understanding and helping to modify the patients’ belief that narcotics are all that can help them; a sound patient-physician relationship and education of the patient about the treatment including opiate detoxification which provides a success rate of 89.7%. A detoxification protocol has been described elsewhere.66
Gallbladder and Sphincter of Oddi Disorders
This category includes biliary pain, functional gallbladder disorder, and functional biliary sphincter of Oddi disorder.67 Biliary pain can occur in the absence of recognized organic causes and some patients are cured by removal of the gallbladder or ablation of the sphincter. In terms of criteria changes for biliary pain disorder from Rome III to Rome IV is only in quantifying the pain. That is not significantly (< 20%) related to bowel movements and/or relieved by postural change or acid suppression. In addition, the occurrence of the pain should not be daily, although this is not evidence based.67
The other changes that have been introduced in Rome IV are in relation to functional biliary sphincter of Oddi disorder. Dysfunction of the sphincter of Oddi (SOD) is commonly considered in patients with biliary-type pain after cholecystectomy, and has been traditionally classified in 3 clinical types of SOD based on manometry and relief with sphincterotomy.67 However, a recent NIH study (EPISOD: evaluating predictors and interventions in sphincter of Oddi dysfunction) has shown that true sphincterotomy is no better than sham sphincterotomy in patients with post-cholecystectomy pain, so that the old concept of SOD Type III is now considered more like functional than biliary related, and endoscopic retrograde cholangiopancreatography approaches are no longer appropriate in that context.68 Furthermore, most patients with SOD Type I have organic stenosis (eg, stones, stricture, pancreatitis, and pancreatic tumor) rather than motility disturbance of the sphincter, and biliary sphincterotomy is recommended; however not in this biliary classification. Therefore, Rome IV now recommends using the term suspected functional biliary sphincter of Oddi disorder for patients with prior SOD Type II only.67
Normal amylase/lipase levels may occur in some pain episodes.67 Also, abnormal biliary manometry was added to the supportive criteria as it has been shown to be a predictor of response to biliary sphincterotomy,69 and hepatobiliary scintigraphy was also included although its value is disputed.67
Anorectal Disorders
Subtle changes were made in this category for Rome IV.70 For Functional Fecal Incontinence, the diagnosis has been changed to a generic one, fecal incontinence.70 In Rome III, chronic proctalgia was subcategorized into levator ani syndrome, unspecified anorectal pain, and proctalgia fugax. Rome IV has retained these three subcategories but has deleted chronic proctalgia as it may include many other conditions.70 Also, the location of pain in proctalgia fugax has been revised to the rectum instead of anal canal or lower rectum.70
Regarding the functional defecation disorders, in the previous classification only patients with functional constipation would be eligible to be diagnosed with a defecatory disorder. However, because it has been recognized that patients with IBS and pelvic floor dysfunction can have an association with dyssynergic dysfunction,71 and they can be treated with biofeedback irrespective of their association with IBS,72 IBS-C have now been included in the Rome IV definition.70 In addition, criteria for inadequate propulsive forces and inappropriate contraction of the anal sphincter and/or pelvic floor muscles are no longer specified because they vary among different techniques.72–74
In patients with functional defecation disorders, the following subcategories apply: inadequate defecatory propulsion defined by inadequate propulsive forces as measured with manometry with or without inappropriate contraction of the anal sphincter and/or pelvic floor muscles; and dyssynergic defecation defined by inappropriate contraction of the pelvic floor as measured with anal surface electromyography or manometry with adequate propulsive forces during attempted defecation.70
Childhood Functional Gastrointestinal Disorders
In the last decade, new insights have been gained about the different DGBI in “neonate/toddlers” and “child/adolescents.” The current criteria are based more on evidence and less on the experts’ experience. DGBI in “neonates and toddlers” include: infant regurgitation, infant rumination syndrome, cyclic vomiting syndrome, infant colic, functional diarrhea, infant dyschezia, and functional constipation.75 Main changes have been introduced in infant colic that has been expanded to include criteria for the general pediatrician and specific criteria for researchers. Also, a section on Neurobiology of Pain in infants and toddlers has been added that addresses the neurodevelopment of nociception and of the wide array of factors that may impact the experience of functional pain. This is contrary to the explanation of the acute pain model that if the pathology of pain is addressed, the pain will dissipate.75
In the “child/adolescent” section, based on the available evidence, the statement “no evidence for organic disease” has been removed from every definition and is now replaced for “after appropriate medical evaluation the symptoms cannot be attributed to another medical condition.”76 Functional nausea and functional vomiting has now been included and in functional dyspepsia, the PDS and EPS subtypes which were not present in Rome III, have now been adopted. Also, the Rome III functional abdominal pain and functional abdominal pain syndrome has now been substituted for Functional Abdominal Pain-Not Otherwise Specified. The frequency required for pain is changed from weekly to 4 times/month to align with other functional abdominal pain disorders (FAPD) and to allow for the inclusion of children who would otherwise not qualify for FAPD. In addition, the wording “that does not occur solely during physiologic events (eg, eating, menses)” has been added to harmonize with the adult criteria. Finally, it has been recognized that DGBI can coexist with other medical conditions such as inflammatory bowel disease.76
Clinical Applications and Resources: Clinical Algorithms, the Multidimensional Clinical Profile, Interactive Clinical Decision Toolkit, and Primary Care
Although the Rome criteria are very useful for clinical research and pharmaceutical trials, they have limitations in clinical practice, as many of our patients do not fulfill all the criteria or the necessary time frame to be diagnosed (sub-threshold disorders), however they would receive equivalent treatments.
“The Rome IV diagnostic algorithms for common gastrointestinal disorders” have been published to meet clinical standards in diagnostic evaluation since the publication of the previous edition 6 years before, and to be consistent with the new Rome IV diagnostic criteria.77 An updated set of diagnostic approaches beginning with common symptoms (eg, abdominal pain, nausea, diarrhea, and constipation) leading to diagnostic testing and ending with diagnosis, is provided. This would be the first part of the clinicians decision in making a diagnosis, and this would be followed by treatment.77
Furthermore, the Multidimensional Clinical Profile (MDCP) has been developed to capture the full dimension of each patient’s clinical presentation and therefore planning an individualized treatment, and is also updated for Rome IV,78 The MDCP is probably the first attempt to a Personalized Medicine approach in the field of DGBI. The MDCP comprises of five categories depicted in Table 4.78 The Rome IV MDCP book included 72 cases to enhance the learning about DGBI and the influence of physiological and psychological factors contributing to the patients clinical presentation. Pediatric and multicultural cases have been included as well.79
| Categories | Examples |
|---|---|
| A. Categorical diagnosis based on Rome IV criteria | |
| B. Clinical modifiers | Bowel habit predominance (ie, IBS-D, IBS-C, IBS-M), post-infection (PI), gluten sensitivity, FODMAPs sensitivity |
| C. Severity impact by self-perception | Mild, moderate, severe |
| D. Psychosocial modifiers and comorbidities | Can be categorical (eg, DSM Axis I), dimensional (eg, HADS, psychosocial red flags), or patient reported (eg, abuse) |
| E. Physiological modifiers and biomarkers of clinical relevance that enhance understanding of the diagnosis | eg, motility, biochemical, antibodies |
Rome has created the Rome IV Interactive Clinical Decision Toolkit, an intelligent software system that addresses the sophistication and complexity of DGBI diagnosis and treatment protocols by providing an online resource to assist practitioners in achieving optimal clinical outcomes. It offers a powerful online and interactive approach for accessing the combination of the Rome IV Diagnostic Algorithms and the MDCP treatment guidelines on-demand and at the point of care. This software will provide both an educational resource as well as a daily guideline to the patients’ individualized diagnosis and treatment. Using any browser-enabled device, physicians and clinicians interact visually with Rome algorithms and guidelines, seeing all relevant decision pathways developed from actual clinical cases and using touch inputs to highlight and activate the pathways that lead to the optimal outcomes and recommendations. The platform operates in the ways that clinicians need to work: by using a logical, multidimensional and yet individualized framework for proper decision making.
Rome IV has also published “The pediatric functional gastrointestinal disorders” book and “The diagnostic questionnaires and tables for investigators and clinicians” book. Finally, recognizing that DGBI are ever present and disorders such as IBS are one of the main reasons for consultation in primary care, Rome IV has published a handbook to help busy primary care physicians on how to diagnose and managed the most common DGBI seen at this level of healthcare.80
Footnotes
Footnote Group
References
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References
- 1.Thompson WG, Dotevall G, Drossman DA, Heaton KW, Kruis W. Irritable bowel syndrome: guidelines for the diagnosis. Gastroenterol Int. 1989:92–95.
- 2.Drossman DA. The Rome IV Committees, editor. History of functional gastrointestinal symptoms and disorders and chronicle of the Rome Foundation. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders: disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016. pp. 549–576.
- 3.Drossman DA, Thompson WG, Talley NJ, Funch-Jeasen P, Janssens J. Identification of subgroups of functional bowel disorders. Gastroenterol Int. 1990;3:159–172.
- 4.Thompson WG, Creed F, Drossman DA, Heaton KW, Mazzacca G. Functional bowel disorders and chronic functional abdominal pain. Gastroenterol Int. 1992;5:75–91.
- 5.Talley NJ, ColinJones D, Koch KL, Koch M, Nyren O, Stanghellini V. Functional dyspepsia: a classification with guidelines for diagnosis and management. Gastroenterol Int. 1991;4:145–160.
- 6.Richter JE, Baldi F, Clouse RE, Diamant NE, Janssens J, Staiano A. Functional oesophageal disorders. Gastroenterol Int. 1992;5:3–17.
- 7.Whitehead WE, Devroede G, Habib FI, Meunier P, Wald A. Functional disorders of the anorectum. Gastroenterol Int. 1992;5:92–108.
- 8.Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38:1569–1580. doi: 10.1007/BF01303162.
- 9.Drossman DA, Richter JE, Talley NJ, Thompson WG, Corazziari E, Whitehead WE. The functional gastrointestinal disorders: diagnosis, pathophysiology and treatment. McLean, VA: Degnon Associates; 1994.
- 10.Thompson WG. The road to rome. Gastroenterology. 2006;130:1552–1556. doi: 10.1053/j.gastro.2006.03.011.
- 11.Drossman DA, Hasler WL. Rome IV-functional GI disorders: disorders of gut-brain interaction. Gastroenterology. 2016;150:1257–1261. doi: 10.1053/j.gastro.2016.03.035.
- 12.Drossman DA, Chang L, Chey WD, Kellow J, Tack J, Whitehead WE The Rome IV Committees. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016.
- 13.Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016;150:1262–1279. doi: 10.1053/j.gastro.2016.02.032.
- 14.Marciani L, Cox EF, Hoad CL, et al. Postprandial changes in small bowel water content in healthy subjects and patients with irritable bowel syndrome. Gastroenterology. 2010;138:469–477.e1. doi: 10.1053/j.gastro.2009.10.055.
- 15.Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702. doi: 10.1053/j.gastro.2003.11.055.
- 16.Barau E, Dupont C. Modifications of intestinal permeability during food provocation procedures in pediatric irritable bowel syndrome. J Pediatr Gastroenterol Nutr. 1990;11:72–77. doi: 10.1097/00005176-199007000-00015.
- 17.Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA. Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology. 1995;109:40–52. doi: 10.1016/0016-5085(95)90267-8.
- 18.van Wijk HJ, Smout AJ, Akkermans LM, Roelofs JM, ten Thije OJ. Gastric emptying and dyspeptic symptoms in the irritable bowel syndrome. Scand J Gastroenterol. 1992;27:99–102. doi: 10.3109/00365529209165425.
- 19.Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut. 1999;44:400–406. doi: 10.1136/gut.44.3.400.
- 20.Camilleri M, Northcutt AR, Kong S, Dukes GE, McSorley D, Mangel AW. Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet. 2000;355:1035–1040. doi: 10.1016/S0140-6736(00)02033-X.
- 21.Kellow J, Lee OY, Chang FY, et al. An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome. Gut. 2003;52:671–676. doi: 10.1136/gut.52.5.671.
- 22.Van Outryve M, Milo R, Toussaint J, Van Eeghem P. “Prokinetic” treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride. J Clin Gastroenterol. 1991;13:49–57. doi: 10.1097/00004836-199102000-00012.
- 23.Sperber AD, Francisconi C, Fukudo S, et al. The Rome IV Committees, editor. Multicultural aspects of functional gastrointestinal disorders. In: Drossman DA, Chang LC, Kellow J, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016.
- 24.Schmulson M, Corazziari E, Ghoshal UC, et al. A four-country comparison of healthcare systems, implementation of diagnostic criteria, and treatment availability for functional gastrointestinal disorders: A report of the Rome Foundation Working Team on cross-cultural, multinational research. Neurogastroenterol Motil. 2014;26:1368–1385. doi: 10.1111/nmo.12402.
- 25.Sperber AD, Gwee KA, Hungin AP, et al. Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report. Aliment Pharmcol Ther. 2014;40:1094–1102. doi: 10.1111/apt.12942.
- 26.Whorwell P, Zarzar K. Conducting multinational, cross-cultural research in the functional GI disorders and fostering multinational research networks. Rome Foundation Working Team; 2014. [accessed 8 March, 2017]. Available from URL: http://theromefoundation.org/wp-content/uploads/WorkingTeamFinal-Report_Jan-2014-1.pdf.
- 27.Francisconi CF, Sperber A, Fang X, et al. Multicultural aspects in functional gastrointestinal disorders (FGIDs) Gastroenterology. 2016;150:1344–1354. doi: 10.1053/j.gastro.2016.02.013.
- 28.Ballard R. Race, culture and ethnicity. In: Holborn M, editor. New developments in sociology. Ormskirk: The Causeway Press; 2002.
- 29.Eisenberg L. Disease and illness. Distinctions between professional and popular ideas of sickness. Cult Med Psychiatry. 1977;1:9–23. doi: 10.1007/BF00114808.
- 30.Gwee KA, Lu CL, Ghoshal UC. Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed. J Gastroenterol Hepatol. 2009;24:1601–1607. doi: 10.1111/j.1440-1746.2009.05984.x.
- 31.Heitkemper MA, Houghton LA, Crowell MD, et al. The Rome IV Committees, editor. Age, gender, and women’s health and the patient. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016. pp. 307–371.
- 32.Quigley EM, Barbara G, Feinle-Bisset C, et al. The Rome IV Committees, editor. The intestinal microenvironment an functional gastrointestinl disorders. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016. pp. 179–247.
- 33.Barbara G, Feinle-Bisset C, Ghoshal UC, et al. The intestinal microenvironment and functional gastrointestinal disorders. Gastroenterology. 2016;150:1305–1318.e8. doi: 10.1053/j.gastro.2016.02.028.
- 34.Levy RL, Crowell MD, Drossman DA, et al. The Rome IV Committees, editor. Byopsychosocial aspects of functional gastrointestinl disorders: How central and environmental processes contribute to the development and expression of FGIDs. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. I. Raleigh, NC: The Rome Foundation; 2016. pp. 443–548.
- 35.Whorwell PJ, Keefer L, Drossman DA, Guthrie E, Simrén M, Tillisch K, Olden K. The Rome IV Committees, editor. Centrally mediated disorders of gastrointestinal pain. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. II. Raleigh, NC: The Rome Foundation; 2016. pp. 1059–1116.
- 36.Keefer L, Drossman DA, Guthrie E, et al. Centrally mediated disorders of gastrointestinal pain. Gastroenterology. 2016;150:1408–1419. doi: 10.1053/j.gastro.2016.02.034.
- 37.Mearin F, Lacy BE, Chang L, et al. Bowel Disorders. Gastroenterology. 2016;150:1393–1407. e5. doi: 10.1053/j.gastro.2016.02.031.
- 38.Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology. 2016;150:1380–1392. doi: 10.1053/j.gastro.2016.02.011.
- 39.Palsson OS, Whitehead WE, van Tilburg MA, et al. Development and validation of the Rome IV diagnostic questionnaire for adults. Gastroenterology. 2016;150:1481–1491. doi: 10.1053/j.gastro.2016.02.014.
- 40.Whitehead EE, Palsson OS, MALvT, Sperber A, BS, Tack J, Walker LS, YY . The Rome IV Committees, editor. Development and validation of the Rome IV diagnostic questionnaires. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV diagnostic questionnaires and tables for investigators and clinicians. Raleigh, NC: The Rome Foundation; 2016. pp. 43–92.
- 41.Schmulson M, Adeyemo M, Gutiérrez-Reyes G, et al. Differences in gastrointestinal symptoms according to gender in Rome II positive IBS and dyspepsia in a Latin American population. Am J Gastroenterol. 2010;105:925–932. doi: 10.1038/ajg.2010.58.
- 42.Ford AC, Marwaha A, Sood R, Moayyedi P. Global prevalence of, and risk factors for, uninvestigated dyspepsia: a meta-analysis. Gut. 2015;64:1049–1057. doi: 10.1136/gutjnl-2014-307843.
- 43.Galmiche JP, Clouse RE, Bálint A, et al. Functional esophageal disorders. Gastroenterology. 2006;130:1459–1465. doi: 10.1053/j.gastro.2005.08.060.
- 44.Savarino E, Marabotto E, Zentilin P, et al. The added value of impedance-pH monitoring to Rome III criteria in distinguishing functional heartburn from non-erosive reflux disease. Dig Liver Dis. 2011;43:542–547. doi: 10.1016/j.dld.2011.01.016.
- 45.Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F. Functional esophageal disorders. Gastroenterology. 2016;150:1368–1379. doi: 10.1053/j.gastro.2016.02.012.
- 46.Bisschops R, Karamanolis G, Arts J. Relationship between symptoms and ingestion of a meal in functional dyspepsia. Gut. 2008;57:1495–1503. doi: 10.1136/gut.2007.137125.
- 47.Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. Gastroenterology. 2006;130:1466–1479. doi: 10.1053/j.gastro.2005.11.059.
- 48.Talley NJ, Stanghellini V, Chan FKL, et al. The Rome IV Committees, editor. Gastroduodenal Disorders. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. II. Raleigh, NC: The Rome Foundation; 2016. pp. 903–965.
- 49.Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simrén M, Spiller R. The Rome IV Committees, editor. Bowel Disorders. In: Drossman DA, Chang LC, Kellow WJ, Tack J, Whitehead WE, editors. Rome IV functional gastrointestinal disorders – disorders of gut-brain interaction. II. Raleigh, NC: The Rome Foundation; 2016. pp. 967–1057.
- 50.Sperber AD, Dumitrascu D, Fukudo S, et al. The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review. Gut. doi: 10.1053/j.gastro.2016.02.014. Published Online First: 13 Feb 2016.
- 51.Spiegel BM, Bolus R, Agarwal N, et al. Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials. Aliment Pharmacol Ther. 2010;32:1275–1291. doi: 10.1111/j.1365-2036.2010.04464.x.
- 52.Hellstrom PM, Saito YA, Bytzer P, Tack J, Mueller-Lissner S, Chang L. Characteristics of acute pain attacks in patients with irritable bowel syndrome meeting Rome III criteria. Am J Gastroenterol. 2011;106:1299–1307. doi: 10.1038/ajg.2011.78.
- 53.Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491. doi: 10.1053/j.gastro.2005.11.061.
- 54.Palson O, van Tilburg M, Simren M, Sperber AD, Whithead W. Mo1642 population prevalence of Rome IV and Rome III irritable bowel syndrome (IBS) in the United States (US), Canada and the United Kingdom (UK) Gastroenterology. 2016;150:S739–S740. doi: 10.1016/S0016-5085(16)32513-6.
- 55.Ghoshal UC, Gwee KA, Chen M, et al. Development, translation and validation of enhanced asian Rome III questionnaires for diagnosis of functional bowel diseases in major asian languages: a Rome Foundation-Asian Neurogastroenterology and Motility Association Working Team Report. J Neurogastroenterol Motil. 2015;21:83–92. doi: 10.5056/jnm14045.
- 56.Morgan D, Martin C, Pena E, et al. Significant differences in Rome II and Rome III determination of FGID prevalence: Population-based assessments in Central America. Gastroenterology. 2012;142(suppl 1):S573. doi: 10.1016/S0016-5085(12)62199-4.
- 57.Schmulson M, Lopez-Colombo A, Mendoza-Gomez A, Montiel-Jarquin A, Morgan D. Tu1426 The Rome III adult questionnaire in Spanish-Mexico has a low sensitivity for identifying IBS and higher sensitivity for uninvestigated dyspepsia. Gastroenterology. 2012;142:S829. doi: 10.1016/S0016-5085(12)63220-X.
- 58.Drossman DA, Morris CB, Hu Y, et al. A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator. Gastroenterology. 2005;128:580–589. doi: 10.1053/j.gastro.2004.12.006.
- 59.Lewis MJ, Reilly B, Houghton LA, Whorwell PJ. Ambulatory abdominal inductance plethysmography: towards objective assessment of abdominal distension in irritable bowel syndrome. Gut. 2001;48:216–220. doi: 10.1136/gut.48.2.216.
- 60.Kalso E, Edwards JE, Moore RA, McQuay HJ. Opioids in chronic non-cancer pain: systematic review of efficacy and safety. Pain. 2004;112:372–380. doi: 10.1016/j.pain.2004.09.019.
- 61.Jamal MM, Adams AB, Jansen JP, Webster LR. A randomized, placebo-controlled trial of lubiprostone for opioid-induced constipation in chronic noncancer pain. Am J Gastroenterol. 2015;110:725–732. doi: 10.1038/ajg.2015.106.
- 62.Argoff CE, Brennan MJ, Camilleri M, et al. Consensus recommendations on initiating prescription therapies for opioid-Induced constipation. Pain Med. 2015;16:2324–2337. doi: 10.1111/pme.12937.
- 63.Drossman DA. 2012 David Sun lecture: helping your patient by helping yourself--how to improve the patient-physician relationship by optimizing communication skills. Am J Gastroentetol. 2013;108:521–528. doi: 10.1038/ajg.2013.56.
- 64.Trivedi MH, Fava M, Wisniewski SR, et al. Medication augmentation after the failure of SSRIs for depression. N Engl J Med. 2006;354:1243–1252. doi: 10.1056/NEJMoa052964.
- 65.Grunkemeier DM, Cassara JE, Dalton CB, Drossman DA. The narcotic bowel syndrome: clinical features, pathophysiology, and management. Clin Gastroenterol Hepatol. 2007;5:1126–1139. doi: 10.1016/j.cgh.2007.06.013.
- 66.Drossman DA, Morris CB, Edwards H, et al. Diagnosis, characterization, and 3-month outcome after detoxification of 39 patients with narcotic bowel syndrome. Am J Gastroenterol. 2012;107:1426–1440. doi: 10.1038/ajg.2012.142.
- 67.Cotton PB, Elta GH, Carter CR, Pasricha PJ, Corazziari ES. Rome IV. Gallbladder and sphincter of oddi disorders. Gastroenterology. 2016;150:1420–1429.e2. doi: 10.1053/j.gastro.2016.02.033.
- 68.Cotton PB, Durkalski V, Romagnuolo J, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014;311:2101–2109. doi: 10.1001/jama.2014.5220.
- 69.Toouli J, Roberts-Thomson IC, Kellow J, Dowsett J, Saccone GT, Evans P, Jeans P, Cox M, Anderson P, Worthley C, Chan Y, Shanks N, Craig A. Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction. Gut. 2000;46:98–102. doi: 10.1136/gut.46.1.98.
- 70.Rao SS, Bharucha AE, Chiarioni G, et al. Anorectal disorders. Gastroenterology. 2016;150:1430–1442.e4. doi: 10.1053/j.gastro.2016.02.009.
- 71.Prott G, Shim L, Hansen R, Kellow J, Malcolm A. Relationships between pelvic floor symptoms and function in irritable bowel syndrome. Neurogastroenterol Motil. 2010;22:764–769. doi: 10.1111/j.1365-2982.2010.01503.x.
- 72.Grossi U, Carrington EV, Bharucha AE, Horrocks EJ, Scott SM, Knowles CH. Diagnostic accuracy study of anorectal manometry for diagnosis of dyssynergic defecation. Gut. 2016;65:447–455. doi: 10.1136/gutjnl-2014-308835.
- 73.Rao SS, Mudipalli RS, Stessman M, Zimmerman B. Investigation of the utility of colorectal function tests and Rome II criteria in dyssynergic defecation (Anismus) Neurogastroenterol Motil. 2004;16:589–596. doi: 10.1111/j.1365-2982.2004.00526.x.
- 74.Ratuapli SK, Bharucha AE, Noelting J, Harvey DM, Zinsmeister AR. Phenotypic identification and classification of functional defecatory disorders using high-resolution anorectal manometry. Gastroenterology. 2013;144:314–322.e2. doi: 10.1053/j.gastro.2012.10.049.
- 75.Benninga MA, Faure C, Hyman PE, St James Roberts I, Schechter NL, Nurko S. Childhood functional gastrointestinal disorders: neonate/ toddler. Gastroenterology. 2016;150:1443–1455.e2. doi: 10.1053/j.gastro.2016.02.016.
- 76.Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional disorders: children and adolescents. Gastroenterology. 2016;150:1456–1468.e2. doi: 10.1053/j.gastro.2016.02.015.
- 77.Drossman DA, et al. In: Rome IV diagnostic algorithms for common GI symptoms. 2nd ed. Kellow J Guest Ed, editor; Raleigh, NC: The Rome Foundation; 2016.
- 78.Azpiroz F, et al. In: Multi-dimensional clinical profile (MDCP) for the functional gastrointestinal disorders. 1st ed. Drossman DA Guest Ed, editor; Raleigh, NC: The Rome Foundation; 2015.
- 79.Drossman DA, Senior Ed, Chang L, et al. Rome IV multidimensional clinical profile for the functional gastrointestinal disorders. 2nd ed. Raleigh, NC: The Rome Foundation; 2016.
- 80.Heidelbaugh J, Hungin P Guest Eds, editors; Drossman DA, Chang L, Kellow J, Chey WD, Tack J, Whitehead WE, editors. The Rome IV Primary Care Committee. Rome IV functional gastrointestinal disorders for primary care and non-GI clinicians. 1st ed. Raleigh, NC: The Rome Foundation; 2016.