Dyspepsia (from the Greek “δυς-” (Dys-), meaning hard or difficult, and “πέψη” (Pepse), meaning digestion) is chronic or recurrent pain or discomfort centered in the upper abdomen ^[1] Discomfort, in this context, includes mild pain, upper abdominal fullness and feeling full earlier than expected with eating. It can be accompanied by bloating, belching, nausea or heartburn. Heartburn is excluded from the definition of dyspesia in ICD 10, as it usually has a different cause and management pathway. Many people get dyspepsia. It is often caused by lifestyle factors, such as smoking and diet, but there are some serious causes such as cancer of the stomach, peptic ulcer disease and some medications. When people have dyspepsia but no risk factors for any of the serious causes, it can be labeled undifferentiated dyspepsia and treated without further investigations. When people have been investigated for dyspepsia but no cause has been found it can be labeled as functional dyspepsia.

Dyspepsia has been recognized as a symptom complex since antiquity, but its mechanisms began to be understood only after peptic ulcer disease became a recognizable clinicopathologic entity. The isolation of Helicobacter pylori by Warren and Marshall in 1982 established that most chronic gastritis and peptic ulcer disease are infectious and curable.^[2] This discovery led to the classification of H. pylori as a group 1 human carcinogen in 1994,^[3] the noninvasive “test-and-treat” strategy for uninvestigated dyspepsia,^[4] and the current framing of H. pylori eradication as a gastric cancer prevention strategy.^[5]

Contemporary classification has moved away from the older dichotomy of “ulcer” versus “non-ulcer” dyspepsia. Patients are now categorized along a three-tier framework: uninvestigated dyspepsia (symptoms present but no diagnostic workup yet performed), organic (secondary) dyspepsia (an identifiable structural, H. pylori-related, metabolic, or drug-induced cause is found), and functional dyspepsia (FD) (no explanatory organic disease is found on evaluation, including a normal upper endoscopy). Functional dyspepsia, as redefined by the Rome IV criteria, is further split into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), which frequently overlap.^[6] More than 70% of patients with uninvestigated dyspepsia ultimately meet criteria for functional dyspepsia rather than organic disease.^[7]

Functional dyspepsia is now classified as a disorder of gut-brain interaction, affecting approximately 7% of the community, and is diagnosed by the presence of one or more of bothersome epigastric pain, epigastric burning, early satiation, and/or postprandial fullness, present for the last 3 months with symptom onset at least 6 months before diagnosis, in the absence of an identifiable organic cause on evaluation including upper endoscopy.^[8] Functional dyspepsia is heterogeneous, with symptoms associated with several overlapping mechanisms: impaired gastric accommodation (~40%), visceral hypersensitivity to gastric distention (~40%), and mild delayed gastric emptying (~30%); approximately 30% of patients have none of these, and these abnormalities correlate poorly with symptoms and occur in asymptomatic controls. Increasing evidence implicates low-grade duodenal microinflammation (modestly increased eosinophils and mast cells with impaired barrier function) driving an aberrant type 2 helper T (Th2) immune response in a subgroup.^[9][10] These mechanisms occur in patients who have acquired excessive responsiveness to stress as a result of the environment during early life, genetic abnormalities, residual inflammation after gastrointestinal infections, or other causes. The process may be modified by factors including psychophysiological abnormalities, abnormal secretion of gastric acid, Helicobacter pylori infection, impaired duodenal mucosal barrier integrity, diet, and lifestyle.

Its causes are divided into two groups:^[6]

• Organic (secondary) dyspepsia: a structural, systemic, metabolic, infectious, or drug-related cause is identified, and symptoms resolve when it is treated.
• Functional dyspepsia (FD): no explanatory disease is found on evaluation.

Approximately 80% of patients with dyspepsia have no structural explanation and are classified as FD.^[9][11] History and examination cannot reliably distinguish organic from functional dyspepsia, and no accurate biomarker exists.^[9][11] The most common organic contributors are gastroesophageal reflux disease, peptic ulcer disease, and NSAID/aspirin use. Myocardial ischemia is the key extra-luminal cause that must not be missed.

Symptoms cannot reliably separate organic from functional dyspepsia, and no single history finding, examination finding, or biomarker distinguishes them. The differential diagnosis is therefore approached in three steps: exclude a limited set of organic mimics, keep myocardial ischemia in mind as the can’t-miss extra-luminal cause, and then apply Rome IV criteria to diagnose functional dyspepsia (FD).^[9] About 80% of patients with dyspepsia have no clinically significant finding at endoscopy. Fewer than 10% have peptic ulcer, and fewer than 0.5% have gastro-esophageal malignancy, so the pretest probability strongly favors FD.^[12] FD must then be distinguished from other disorders of gut–brain interaction (DGBI) and from the chronic nausea and vomiting disorders it overlaps with.^[13]

Dyspepsia is one of the most common upper gastrointestinal symptom complexes. Its frequency depends heavily on how it is defined. Uninvestigated dyspepsia (upper GI symptoms without prior endoscopy) affects approximately 21% of adults worldwide, and about 80% of these individuals have no organic cause at endoscopy.^[14][9] Functional dyspepsia is a disorder of gut–brain interaction defined by Rome criteria.^[6] Rome-criteria functional dyspepsia has a global pooled prevalence of 8.4%.^[15] Under Rome IV criteria, the prevalence is 7.2% worldwide and 10.1% in the United States, with an annual incidence of approximately 3–4%.^[16][13] Functional dyspepsia is more common in women and in adults younger than 40 years. Its prevalence has declined over the past three decades, partly because successive Rome criteria have become stricter.^[15][13] Postprandial distress syndrome accounts for about two-thirds of cases. Overlap with irritable bowel syndrome and other disorders of gut–brain interaction is common. Functional dyspepsia also carries substantial healthcare utilization and economic burden.^[16][9]

Risk factors for the development of dyspepsia are multifactorial and include Helicobacter pylori infection, chronic use of NSAIDs, family history of peptic ulcer disease, prior acute gastroenteritis (post-infectious dyspepsia), emotional stress and psychological comorbidity (particularly anxiety and depression), female sex, tobacco smoking, and dietary factors including increased intake of high-fiber, high-fat, and greasy foods and overconsumption of caffeine.^[6][14] A large meta-analysis of population-based studies found that the prevalence of uninvestigated dyspepsia was significantly higher among women, smokers, NSAID users, and individuals who were H. pylori-positive.^[14] A single Mendelian randomization study provides emerging, genetically-supported evidence for depression and gastroesophageal reflux disease as risk factors for functional dyspepsia; this inference rests on genetic-instrument assumptions and requires replication.^[17] The relationship with body mass index is bidirectional: higher BMI is the more consistent independent predictor of incident functional dyspepsia in longitudinal and large global data, while underweight/leanness is associated with functional dyspepsia in several Asian and primary-care cohorts, and a U-shaped relationship confined to women has been described. Alcohol consumption is a less consistent association. Age ≥60 years is the dominant risk marker for underlying organic or malignant disease and, per the 2017 ACG/CAG guideline, warrants upper endoscopy; alarm features (unintentional weight loss, gastrointestinal bleeding, dysphagia, persistent vomiting, family history of upper GI malignancy) raise concern but do not by themselves mandate endoscopy in patients under 60.^[4]

There is insufficient evidence to recommend routine screening for Dyspepsia.

FD is a chronic, relapsing-remitting disorder of gut-brain interaction (DGBI). Its symptoms fluctuate over years, and it frequently overlaps with or converts to irritable bowel syndrome (IBS) and gastroesophageal reflux disease (GERD).^[9][13] FD does not progress to structural disease, and longitudinal data show normal life expectancy. However, FD substantially impairs quality of life and carries a heavy burden of psychological comorbidity. Recent data also link FD to increased risks of hospitalization and death.^[18][13] Serious complications arise almost entirely from organic causes. These include peptic ulcer disease, ulcer-related bleeding and iron deficiency anemia, and upper gastrointestinal (GI) malignancy. Upper GI cancer is found in only a small minority of patients with dyspepsia, and approximately one in four of those cancers presents without alarm features.^[19] In organic dyspepsia, prognosis depends on age- and risk-based endoscopy triage. It also depends on eradicating Helicobacter pylori, which heals and prevents peptic ulcers and reduces the incidence of and mortality from gastric cancer.^[4][20]

The history in dyspepsia has three purposes: (1) confirm that symptoms are epigastric-predominant rather than heartburn-predominant; (2) screen for alarm features and age/risk factors that direct endoscopy; and (3) identify culprit medications and H. pylori risk. Symptom pattern alone discriminates poorly between functional and organic causes and should not be used to make an etiologic diagnosis.^[9][21]

The physical examination in dyspepsia is usually normal, and no examination finding reliably distinguishes functional dyspepsia (FD) from organic causes such as peptic ulcer disease, gastroesophageal reflux disease, or upper gastrointestinal malignancy.^[9][22] Mild epigastric tenderness is the most common finding but is nonspecific.^[23] The examination has two main purposes: to detect findings that fall outside the FD spectrum (a palpable mass, lymphadenopathy, organomegaly, jaundice, an acute abdomen, or signs of gastrointestinal blood loss), which redirect the diagnostic pathway, and to elicit Carnett’s sign, which distinguishes chronic abdominal-wall pain from visceral pain and can spare unnecessary gastrointestinal testing.^[9][22]

There is no diagnostic laboratory test for dyspepsia itself. Laboratory evaluation serves three purposes: to detect anemia or other findings that redirect the diagnosis away from functional dyspepsia (FD), to establish Helicobacter pylori status for a test-and-treat strategy and to confirm eradication, and, in selected patients, to investigate uncommon organic causes such as Zollinger-Ellison syndrome (ZES).^[21][10] Current guidance favors a targeted approach; reflexive laboratory panels are low-yield, costly, and may reinforce illness behavior.^[21][10]

Medical therapy for dyspepsia is stepwise, empiric, and symptom-directed. The same treatment sequence applies to uninvestigated dyspepsia and to functional dyspepsia (FD) once organic disease has been excluded: Helicobacter pylori test-and-treat, then a time-limited proton pump inhibitor (PPI) trial, then a central neuromodulator, then a prokinetic, with psychological therapy for non-responders. H. pylori eradication and empiric PPI therapy both carry strong ACG/CAG recommendations; eradication is the only therapy that is potentially disease-modifying, since sustained benefit reclassifies the patient as having H. pylori-associated dyspepsia. Effect sizes across all effective therapies are modest.^[4][10]

Surgery has a limited, narrowly defined role in dyspepsia and is directed almost exclusively at complications of organic disease — principally peptic ulcer disease (PUD) complicated by perforation, refractory haemorrhage, or gastric outlet obstruction, rather than at functional dyspepsia (FD) itself.^[24] Contemporary guidelines, including the British Society of Gastroenterology (BSG) 2022 guideline, explicitly recommend against surgery for refractory FD given the absence of high-quality evidence of benefit and the recognised risk of iatrogenic harm.^[8][13] The marked decline in elective peptic ulcer surgery over recent decades reflects the success of H. pylori eradication and proton pump inhibitor therapy.^[24][25] Procedural interventions such as gastric peroral endoscopic myotomy (G-POEM) and gastric electrical stimulation (GES) are established only in the context of scintigraphically confirmed gastroparesis, not FD per se.^[26]

Primary prevention of dyspepsia targets three modifiable domains: eradication of Helicobacter pylori, prevention of NSAID– and aspirin-related mucosal injury, and lifestyle modification.^[9][27][24] Prevention of organic dyspepsia (peptic ulcer disease, H. pylori-associated dyspepsia, gastric cancer) is supported by stronger evidence than prevention of functional dyspepsia (FD), for which the benefit of lifestyle and dietary measures remains disputed.^[9][13] H. pylori eradication is the only intervention with disease-modifying potential across PUD, gastric cancer, and dyspepsia.^[28][20]

Secondary prevention of dyspepsia aims to prevent symptom relapse and recurrence of the underlying lesion in patients who have already been diagnosed and treated. This includes treated uninvestigated dyspepsia, treated functional dyspepsia (FD), treated Helicobacter pylori-associated dyspepsia, and healed peptic ulcer disease (PUD). FD is a disorder of gut–brain interaction with a chronic, relapsing–remitting course.^[21][4] The main secondary prevention measures are:

• Confirmed and sustained H. pylori eradication
• The lowest effective acid suppression, with periodic deprescribing
• Removal or mitigation of NSAID exposure
• Psychological therapy and central neuromodulators for relapsing FD