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
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
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.13Table 1 summarizes the Rome IV process.
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.
Although the word
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
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
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
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
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
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.
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,
It must be noted that
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
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
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
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.
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
This category includes 2 disorders,
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
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
This category includes
The other changes that have been introduced in Rome IV are in relation to
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
Subtle changes were made in this category for Rome IV.70 For Functional Fecal Incontinence, the diagnosis has been changed to a generic one,
In patients with functional defecation disorders, the following subcategories apply:
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
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
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
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