The Rome criteria, which define disorders of gut-brain interaction (DGBIs), are extensively applied in epidemiologic research, pathophysiologic studies, treatment trials, and clinical practice. The requirement for long periods of symptom presence and high symptom frequencies facilitated the use of the Rome criteria in epidemiology studies and treatment trials but has hampered clinical application when these requirements were not fulfilled. The Rome Foundation proposes a modification of the diagnostic criteria for clinical practice, where a DGBI diagnosis can still be made if (1) the nature of the symptoms corresponds to those in the DGBI Rome IV diagnostic criteria and (2) the symptoms are bothersome (interfering with daily activities or requiring attention, causing worry or interference with quality of life). If this is the case, a lower frequency and a shorter duration (8 weeks or more) than those required for the Rome DGBI diagnostic threshold are allowed, provided that there is clinical confidence that other diagnoses have been sufficiently ruled out based on presentation and additional investigations as needed. Applying these criteria for clinical practice will allow the clinician to make a diagnosis, reduce unnecessary diagnostic studies, and enhance the patient-provider relationship. Further research is needed to validate these recommendations. DGBIs formerly known as functional gastrointestinal disorders, are characterized by clusters of symptoms. Their pathophysiology relates to any combination of altered motility, visceral sensitivity, epithelial barrier, mucosal immune function, microbiota, or gut–central nervous system neural processing. As such, routine investigations identify no underlying structural abnormality that readily explains the symptoms. The development of symptom-based criteria arose more than 3 decades ago because of the need to identify patients who had gastrointestinal symptoms for which there was no mechanistic explanation for diagnosis in clinical practice and for selection in clinical trials for DGBIs because there was no criterion standard or biomarker. Using irritable bowel syndrome (IBS) as the prime example, in the 1980s, pharmaceutical companies became interested in targeting this disorder for treatment. However, there was no diagnostic standard, and clinically, diagnosis was made by exclusion. A 1988 review of clinical trials for IBS found that entry criteria varied to the degree that patients would enter with and without abdominal pain, or some would have diarrhea and others, constipation. The author concluded that not a single IBS treatment trial reported to date has used an adequate operational definition of IBS. During this period, investigators were doing epidemiologic and factor analytic studies to characterize normal and abnormal bowel habit, , and performing clinical studies to distinguish patients with IBS from those with other diseases. Using these data, a group of experts formed a working team to create diagnostic criteria by consensus using a Delphi approach,, 8 The WTR’s, the Delphic oracle and the Roman conclaves. and the first consensus-based diagnostic criteria for IBS were published.9
Irritable bowel syndrome: guidelines for the diagnosis. Subsequently, additional working teams were formed to develop a classification system for all of the DGBIs based on regional anatomy (esophageal, gastroduodenal, bowel, biliary, and anorectal). 10
Identification of subgroups of functional bowel disorders. This work resulted in the creation of the Rome Foundation, which in 1994 published the first book characterizing and classifying patients with these disorders (now called Rome I).11
The functional gastrointestinal disorders: diagnosis, pathophysiology and treatment. This process continued with Rome II (2000), Rome III (2006), and Rome IV (2016). Currently, with Rome IV, there are 33 adult and 17 pediatric DGBIs, and validation studies support their use., ,14
Validation of Rome criteria for functional gastrointestinal disorders by factor analysis. ,15
Development and validation of the Rome III diagnostic questionnaire. , ,17
Validation of the pediatric Rome II criteria for functional gastrointestinal disorders using the questionnaire on pediatric gastrointestinal symptoms.
Since their acceptance by research and regulatory agencies, the concept of symptom-based criteria has stood the test of time over 3 decades. They remain clinically useful and are promoted in clinical and educational programs and curricula by allowing for a “positive” diagnosis rather than exclusion, the method that preexisted these criteria. As the Rome criteria became more established over time for research, clinicians began to debate their use for clinical practice., , 21
Rome III, Rome IV, and potential Asia symptom criteria for functional dyspepsia do not reliably distinguish functional from organic disease.
23
Comparison of the Rome IV criteria with the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care.
An example is if the patient meets the qualitative symptom criteria, but the symptoms have existed for less time than the Rome criteria require. For research purposes, the Rome IV criteria require symptom onset 6 months before the diagnosis and symptoms meeting the Rome IV criteria to have been present during the previous 3 months to exclude the possibility of other diagnoses. This approach increases the reliability of patient selection for epidemiologic studies. It also ensures adequate time to exclude other diagnoses and provide sufficient symptom duration for treatment trials that require symptoms to be present for several months. However, in the clinical setting, patients may be adequately evaluated within a shorter time. This would occur with a patient presenting with chest pain repeatedly over several weeks when the cardiologic and gastroenterological investigations have determined a likely esophageal cause. However, a strict application of the Rome IV diagnostic criteria for functional chest pain requires a symptom history of 6 months. Furthermore, in Asia, prompt endoscopy is a rule for individuals with dyspeptic symptoms. The majority of patients may consult a physician as early as 1 month after the appearance of dyspeptic symptoms. This highlights the need to diagnose at the time of a negative endoscopy result, as demonstrated in Asian publications. However, the more extended time requirement of the Rome criteria has been implicated in the observation that most patients with epigastric symptoms and negative endoscopy results are diagnosed with chronic gastritis., 27
Systematic review with meta-analysis: prompt endoscopy as the initial management strategy for uninvestigated dyspepsia in Asia.
Also, the frequency of the symptoms occurring in clinical settings may be less than the stated criteria. For example, with Rome IV, the frequency thresholds were based on a strict application of epidemiologic data (90th percentile). However, frequencies out of this threshold may still affect the patient’s quality of life or functioning, making it highly desirable for a diagnosis and targeted treatment to be made. Examples include cyclic vomiting syndrome, biliary pain, or abdominal migraine (in children). As the Rome criteria’s impact grew with time, they were also applied in some settings for billing purposes, which restricted reimbursement for services if patients had symptoms not (yet) meeting the duration requirements. 28 Farmacotherapeutisch rapport linaclotide (Constella®) bij de indicatie symptomatische behandeling van matig tot ernstig prikkelbaredarmsyndroom met constipatie (PDS-C) bij volwassenen. The discrepancy between the Rome research criteria and clinical diagnoses became even more prominent with the publication of the Rome IV criteria, where changes in specific parameters compared to Rome III made the diagnosis less prevalent and defined a population with more severe disease., 21
Rome III, Rome IV, and potential Asia symptom criteria for functional dyspepsia do not reliably distinguish functional from organic disease.
23
Comparison of the Rome IV criteria with the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care.
30
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.
Based on the emerging discrepancy between the Rome criteria and their clinical application, by consensus of the Rome Foundation Board of Directors, we developed a modification for the Rome IV diagnostic criteria in clinical practice. We propose 4 factors to consider when offering recommendations for clinical criteria. Using these guidelines provides the opportunity for clinicians to rule out other diagnoses sufficiently. Clinicians will evaluate symptom patterns, risk factors, and other patient characteristics to select additional investigations if needed. If all elements are in keeping with a DGBI diagnosis, the diagnosis can be made with confidence despite a lower frequency and duration. We recommend that the following be fulfilled to meet the Rome Foundation clinical criteria: The use of these criteria assumes that other diagnoses have been sufficiently ruled out based on the clinical presentation and additional investigations when needed. These criteria do not replace the standard Rome IV criteria for clinical trials or epidemiologic or pathophysiologic studies. The Rome Foundation believes that applying these criteria for clinical practice and communicating the diagnosis with confidence will improve patient acceptance, reduce unnecessary diagnostic studies, and enhance the patient-provider relationship. The Foundation also plans to determine the relevance of clinical criteria in clinical practice studies and determine their impact on patient and provider satisfaction, health outcomes, and costs. Future research will need to address whether any minimal thresholds in terms of the bothersomeness, frequency, and duration of symptoms can be identified for clinical practice criteria for specific DGBIs. The type and number of additional investigations that are useful for the evaluation of symptoms with a shorter history of onset also will need to be evaluated and may lead to recommendations for specific DGBIs. The clinical criteria proposed can serve as a basis for studies to validate their application in clinical practice. The data from future studies will then be applied and implemented in the upcoming Rome V consensus. The existing duration and frequency criteria continue to be required for epidemiologic research, pathophysiologic studies, and therapeutic trials in DGBIs. The Board of Directors of the Rome Foundation provided input to the study concept and design and critical revision of the manuscript. The authors would like to thank the members of the Rome Foundation Board of Directors for their contributions to this document: Giovanna Barbara, MD; Lin Chang, MD; William D. Chey; Xiucai Fang, MD; Laurie Keefer, PhD; Brian E. Lacy, MD, PhD; Samuel Nurko, MD; Max J. Schmulson W. MD; Magnus Simren, MD, PhD; and Ami Sperber, MD, MSPH.
Published online: November 19, 2021 Conflicts of interest The authors disclose no conflicts. Funding This work was funded by the Rome Foundation. DOI: https://doi.org/10.1053/j.gastro.2021.11.019 © 2022 by the AGA Institute. Published by Elsevier Inc. |
