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Mini Review

Dig Dis 2017;35:14–17 Published online: February 8, 2018
DOI: 10.1159/000485408

Functional Dyspepsia and Irritable Bowel
Syndrome: Beyond Rome IV
Vincenzo Stanghellini
Policlinico S. Orsola-Malpighi, University of Bologna, Bologna, Italy

Keywords procedures fail to identify any organic, systemic or meta-
Functional gastrointestinal disorders · Rome criteria · bolic cause that is responsible for digestive function ab-
Classification · Diagnosis · Treatment approach normalities and symptom perception, so that these con-
ditions are classified as functional gastrointestinal disor-
ders (FGIDs; Fig.  1). Although only about 25% of
Abstract symptomatic individuals seek medical support, FGIDs
Background: The correct diagnosis of functional gastroin- represent 40% of diagnoses in gastroenterological set-
testinal disorders (FGIDs) is quite a challenge. The overlaps tings [1], and they are one of the leading causes for refer-
between syndromes can complicate the interpretation of ral to emergency care units [2], thus draining substantial
clinical data. Summary: The incidence of functional diges- amounts of healthcare resources. Functional dyspepsia
tive disorders and irritable bowel syndrome are still under- (FD) and irritable bowel syndrome (IBS) are the most
estimated with the currently applied diagnostic tools, and common FGIDs. The lack of non-invasive, cheap, read-
the management of the seemingly elusive disease is not sat- ily available biomarkers for diagnosing FD and/or IBS
isfactory. For this reason, the “Rome” criteria were created to makes doctors still uncertain about the clinical approach
provide a better understanding and classification of FGIDs. to these conditions, despite major advancements in the
Key Messages: Rome diagnostic criteria and recommenda- understanding of their pathophysiological mechanisms
tions should be used in the design and performance of clin- and relative therapeutic improvements in the last de-
ical studies in the field of functional dyspepsia and irritable cades. Thus, a series of traditional diagnostic investiga-
bowel syndrome. © 2018 The Author(s) tions are often performed and repeated despite negative
Published by S. Karger AG, Basel findings, thus failing to provide appropriate explana-
tions of the nature of symptoms and leaving patients
frustrated and worried about their “strange” clinical
problems. As a consequence, patients end up seeking
Incidence of Functional Gastrointestinal Disorders new (often similarly useless) consultations [3, 4]. The re-
cently updated Rome IV criteria were designed not only
Digestive symptoms are frequent in the general popu- to provide guidance for research studies in general and
lation, ranging between 10 and 30 per cent in industrial- therapeutic trials in particular, but also to facilitate mak-
ized countries, although with highly variable degrees of ing a positive diagnosis of individual FGIDs, based on
severity. In the majority of cases, traditional diagnostic both, presence of characteristic symptoms and absence

© 2018 The Author(s) Prof. Dr. Vincenzo Stanghellini
Published by S. Karger AG, Basel Policlinico S. Orsola-Malpighi, University of Bologna
Via Albertoni 15
E-Mail karger@karger.com This article is licensed under the Creative Commons Attribution-
NonCommercial-NoDerivatives 4.0 International License (CC BY- IT–40138 Bologna (Italy)
www.karger.com/ddi E-Mail v.stanghellini @ unibo.it
NC-ND) (http://www.karger.com/Services/OpenAccessLicense).
Usage and distribution for commercial purposes as well as any dis-
tribution of modified material requires written permission.

Cannabinoid hyperemesis syndrome • C. Esophageal disorders – A1. The pathophysiology of FD is multifactorial and not satisfactory or early relapses occur. Centrally mediated disorders of gastrointestinal pain • E. Levator ani syndrome • F2b. Functional heartburn Diagnostic criteria based on – A3. toms of patients diagnosed with H. of alarm features. Postprandial distress syndrome (PDS) • B1b. low-grade Functional Dyspepsia and Irritable Bowel Dig Dis 2017. and epigastric burning that are severe enough to epigastric pain or epigastric burning that do not neces- to interfere with the usual activities and occur at least 3 days sarily occur after meal ingestion. signs [6]. and on objective findings from a lim. whom no identifiable explanation for the symptoms can be detected by traditional diagnostic procedures are diag- nosed as being affected by FD. Excessive supragastric belching • B2b. Symp. pylori associated dys- ited number of standard diagnostic tests and investiga. (2) epigastric pain syndrome (EPS). Schematic representation of functional gastrointestinal disorders according to the Rome IV criteria [6]. Gastroduodenal motor and sensory dys- for Helicobacter pylori infection is recommended. may occur during fasting per week over the last 3 months with an onset of at least and can be even improved by meal ingestion. Reflux hypersensitivity symptoms that are not explained by – A4. early satiety. Functional abdominal bloating/distension – C5. Functional gastrointestinal disorders (FGID) – Rome IV • A. Functional pancreatic SO disorder • F. Functional diarrhea – C4. Cyclic vomiting syndrome (CVS) • B3c. disturbance. in the absence of alarm symptoms and be distinguished from gastro-esophageal reflux disease.35:14–17 15 Syndrome DOI: 10. The umbrella term “FD” Rome Diagnostic Criteria and Differential Diagnosis comprises patients from the following categories: (1) post- prandial distress syndrome (PDS) that is characterized by The Rome IV criteria define dyspepsia as any combina. Biliary pain • E1a. Functional defecation disorders • F3a. that refers gastric pain. a test and treat approach fully understood. Chronic nausea and vomiting syndrome (CNVS) • B3b. Patients in tions [5. Functional constipation – C3. patients are diagnosed as being affected by unin. epi. Opioid induced constipation • D. If the response is un. Irritable bowel syndrome – C2. characterized by meal- vestigated dyspepsia and can be treated empirically on the induced dyspeptic symptoms and epigastric pain or burn- basis of their clinical manifestations. Functional chest pain – A2. Inadequate defecatory propulsion • F3b. 1. Gastroduodenal disorders – B1. is reminiscent 6 months in advance [7]. Functional dysphagia • B. Nausea and vomiting disorders • B3a. Excessive gastric belching – B3. Proctalgia fugax – F3. Unspecified functional bowel disorder – C6.1159/000485408 . Bowel disorders – C1. After an accurate history taking of the clinical features typical of a peptic ulcer and needs to and physical exam. Functional biliary SO disorder – E2. 6]. Anorectal disorders – F1. Epigastric pain syndrome (EPS) – B2. Globus any detectable disease – A5. Belching disorders • B2a. Functional anorectal pain • 6 principal domains • F2a. Dyssynergic defecation Fig. pepsia are treated by H. Gallgallbladder and sphincter of oddi (SO) disorders – E1. Fecal incontinence FGIDs in adults – F2. Functional dyspepsia • B1a. Unspecified functional anorectal pain • 27 disorders • F2c. pylori eradication. meal-induced dyspeptic symptoms suggestive of a motility tion of 4 symptoms: postprandial fullness. and (3) overlapping PDS and EPS. Functional gallbladder disorder • E1b. ing. function as well as impaired mucosal integrity.

duodenal eosinophilia and motor disorders) and symptom perception at the cen- has been reported in FD patients. (2) IBS-D with predominant diarrhea (i.1159/000485408 . pylori associated gastritis. and dysregulation of the gut-brain axis or 2). >25% of physical stressors expose the largest immune system of the bowel movements with Bristol stool form types 1 or 2 and human body. acid. to an- <25% of bowel movements with Bristol stool form types 6 tigenic activation. bowel movements with Bristol stool form types 6 or 7 and prostanoids. but they corre. al interaction mechanisms between central and peripheral cated in the pathogenesis of duodenal mucosal inflamma. The underlying pathophysiological mechanisms lipids and other intraluminal stimuli can be found in sub. as crine factors potentially involved include abnormal release well as physical and emotional abuse and difficulty in cop. vate changes in digestive functions (including secretory yond H. Bacte- Subforms of IBS rial and viral pathogens responsible for infectious gastro- enteritis represent the strongest known risk factor for the The term IBS defines a syndrome characterized by re. Moreover. which in turn acti- submucosal immune system to luminal noxious agents. irrespective of bowel habits. frequently present. smoking and food allergy have all been impli. In. di- ent during the last 3 months [10]. development of IBS (post-infectious IBS or PI-IBS). A cor- current abdominal pain in association with altered bowel relation between gut dysbiosis and expression of several habits (diarrhea. Specifically. mechanisms are likely involved [9]. grossly resemble those described for FD. or 7). depression. suggesting potential new tral nervous system level. Post-infectious dyspepsia also seems to play a relevant role in polymorphisms detect- has been reported.e. roides ratio and a decreased diversity of bacterial species seem to be of major relevance among the several abnor- malities identified in subgroups of patients with IBS. Infections. A pivotal role is played by acti- <25% of bowel movements with Bristol stool form types 1 vated mast cells which are increased in the subsets of IBS 16 Dig Dis 2017. are frequent among dyspeptic patients. Genetic predisposition tory and permeability changes. Increased mucosal per- most often prompt modifications in the usual activities of meability probably modulated by genetic factors. or both). com. but are not included in the diagnostic as well as ingestion of excessive amounts of fermentable definition of IBS.. and (4) unclassified IBS-U describing those patients dation and abnormally distended antrum. stress. According to the host gene pathways controlling cell junction integrity and Rome IV criteria. and host-microbiota interaction [13].e. including histamine. ing with life events. thus inducing the release of a cascade of or 7). The main motor abnormalities bowel movements with Bristol stool form types 1 or 2 and include delayed gastric empting and impaired distribution >25% of bowel movements with Bristol stool form types 6 of gastric contents with inhibited gastric fundus accommo. including IBS. its cannot be categorized into any of the three previous Gastric and duodenal hypersensitivities to distension. who meet diagnostic criteria for IBS but whose bowel hab- late only partially with symptoms’ quality and severity. but are roles in the subsets of IBS patients. ed in genes involved in immune activation. and proteases. An increased Firmicutes/Bacte- to develop psychological problems [9]. constipation.. and severity of carbohydrates are thought to play relevant pathogenetic symptoms range from negligible to incapacitating. Psychosocial disorders rier. Be. Abdominal bloating and/ etary factors may also be involved in the determination of or distension or other forms of abdominal discomfort are the syndrome. and excessive stimulation of submucosal EPS patients present decreased gastric compliance. immune system are involved in the stimulation of both in- creased permeability of the mucosal barrier exposes the trinsic and extrinsic neural pathways. and symptoms should be pres.35:14–17 Stanghellini DOI: 10. lactose and gluten sensitivities. therapeutic approaches. Development of A bidirectional relationship probably exists between gut molecular techniques is promoting a rapid increase in our and psyche: studies on the natural history of FGIDs suggest understanding of gut microbiota in several pathological that patients affected by FD and IBS are particularly prone conditions. duodenal acid as previously mentioned. abnormalities in the bi-direction- exposure. epithelial bar- pared to post-infectious IBS [8]. by aggressive intraluminal contents and psychological or (1) IBS-C with predominant constipation (i. although it seems to be short-lived. insufficient and postprandial gastric hyper-mechanosensitivity. IBS is subclassified into 4 categories. duration. >25% of have all been implicated [7]. both during fasting and after meals [9]. neuroticism. while mucosal barrier. since an abnormal sets of dyspeptics. cytokines.. as well as affected individuals. of serotonin in IBS patients. (3) IBS-M with mixed bowel habits (i. groups. PDS patients are characterized by fasting interplay among aggressive luminal contents. As long suspected by patients and doctors alike. symptom onset should occur at least inflammatory response has been detected in PI-IBS and 6 months before diagnosis. Frequency. which is located in the gut submucosa.e. IBS-D. Enteroendo- may also play a role: anxiety. respectively [11. >25% of inflammatory mediators. 12].immune activation.

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