Functional dyspepsia

doi:10.1016/S0140-6736(20)30469-4

The Lancet

Volume 396, Issue 10263, 21–27 November 2020, Pages 1689-1702

https://doi.org/10.1016/S0140-6736(20)30469-4 Get rights and content

Summary

Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.

Introduction

The prevalence of dyspepsia in the general population is approximately 20%.¹ 80% of these individuals have no explanation for their symptoms at endoscopy and have functional dyspepsia.² Therefore, overall, the prevalence of functional dyspepsia is approximately 16%, but might vary according to country and criteria used to define its presence. Characteristic symptoms include epigastric pain, epigastric burning, postprandial fullness, or early satiety, present for at least 6 months.³ Functional dyspepsia is a chronic functional disorder of the gastrointestinal tract with no cure; therefore, it affects quality of life and social functioning.4, 5 Treatment approaches include eradication of Helicobacter pylori, if the infection is present; acid suppression therapy; prokinetic drugs; and central neuromodulators. The economic impact is estimated to be over US$18 billion per year in the USA.⁶

Section snippets

Epidemiology

The symptom-based criteria in current use for functional dyspepsia are the Rome IV criteria, which were developed by a group of experts in functional gastrointestinal disorders, and are in their fourth iteration.³ The Rome IV criteria divide functional dyspepsia into two subgroups: epigastric pain syndrome and postprandial distress syndrome (table 1). These subgroups were established because of the predominance of meal-related symptoms observed in some patients⁷ and clustering of particular

Risk factors

Numerous epidemiological studies show that female sex, smoking, use of non-steroidal anti-inflammatory drugs, and H pylori infection are associated with dyspepsia in the general population, but the magnitude of these associations is modest.¹ However, the Kyoto consensus suggests that infection with the H pylori bacterium is an organic cause of dyspepsia, termed H pylori-associated dyspepsia.²⁶ Nevertheless, this term is contentious as the consensus also states that if symptoms persist or recur

Pathophysiology

Despite extensive research, and because of the multifactorial nature and heterogeneity of symptoms in functional dyspepsia, the condition's underlying pathophysiology remains unclear. Symptom generation is part of a complex relationship between the gastroduodenal region of the gut and the brain, triggered by factors including food, stress, and psychosocial comorbidities (figure 2). There are published disease models proposing that all of these factors could fit with a single pathogenesis.³⁷

Clinical presentation and differential diagnosis

Diagnosing functional dyspepsia confidently can be difficult for physicians due to unfamiliarity with its epidemiology, cardinal symptoms, comorbid conditions, and diagnostic criteria. Just as importantly, it is unlikely that a patient will arrive at a consultation announcing that they have the disorder. Additionally, the symptoms of functional dyspepsia are indistinguishable from those of dyspepsia with potentially organic causes (panel). To overcome these impediments to an accurate diagnosis,

Investigations

Unfortunately, history and clinical examination cannot accurately distinguish functional dyspepsia from organic causes of dyspepsia,⁹⁴ and no accurate biomarker is available to facilitate the diagnosis. A validated diagnostic algorithm does not exist, and neither the Rome committee nor current guidelines support routine laboratory testing in all patients.3, 84 A full blood count should probably be requested because a diagnosis of anaemia might change the overall diagnosis. If there is concern

Natural history and effect

The incidence of functional dyspepsia is 3–5% per year.27, 101 Population-based longitudinal studies show that prevalence is relatively stable over time, between 13% and 16% in two studies from Scandinavia with 10 year follow-up.29, 101 The long-term natural history is that of a chronic fluctuating disorder, with approximately 50% of individuals having persistent symptoms, 10–20% having symptom resolution, and 30–40% having a change of symptoms to either IBS, gastro-oesophageal reflux, or a

Management

Management of functional dyspepsia includes reassurance that there is no structural cause for the symptoms; explanation of the pathophysiology and natural history of the disorder; and treatment directed towards the predominant symptom, or symptoms, with realistic discussion of limitations of available therapies to manage expectations. Little evidence exists to suggest that lifestyle changes or exercise lead to symptom improvement and, although some foods are implicated in the generation of

Future directions and controversies

Despite wide acceptance of the Rome IV criteria, functional dyspepsia continues to be underdiagnosed and confused with gastroparesis, even by experts.86, 131 Biomarkers to discriminate functional dyspepsia from other disorders with similar or overlapping symptoms are needed, rather than relying only on symptom-based criteria and a negative endoscopy. Duodenal eosinophilia is now an established biomarker linked to symptoms of postprandial distress syndrome, particularly early satiety.62, 63

Search strategy and selection criteria

We searched MEDLINE, Embase, Embase Classic, and the Cochrane Central Register Of Controlled Trials for articles published during the past 10 years using the terms “functional dyspepsia”, “non-ulcer dyspepsia”, “epidemiology”, “prevalence”, “incidence”, “aetiology”, “pathophysiology”, “diagnosis”, “investigation”, “management”, “therapy”, AND “treatment” to identify relevant publications. Additionally, we searched national guidelines for the management of dyspepsia and ClinicalTrials.gov for

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