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Definition
Dyspepsia is derived from the Greek words “δυς-” (dys-) and “πέψη” (pepse) and literally means “difficult digestion.” In current medical terminology, dyspepsia refers to a heterogeneous group of symptoms in the upper abdomen. In the literature, dyspepsia is often broadly defined as pain or discomfort centered in the upper abdomen but may include multiple and varying symptoms such as epigastric pain, postprandial fullness, early satiation, anorexia, belching, nausea and vomiting, upper abdominal bloating, and even heartburn and regurgitation. Patients with dyspepsia commonly report several of these symptoms.
Several consensus definitions for dyspepsia and functional dyspepsia (FD) have been proposed, with the Rome Consensus Committees providing the most influential classifications. With time, definitions of dyspepsia have evolved to become more restrictive and focused on symptoms that are thought to arise from the gastroduodenal region, not the esophagus.
Earlier definitions considered dyspepsia to comprise all upper abdominal and retrosternal sensations—in effect, all symptoms considered to be referable to the proximal alimentary tract. The Rome I and II Consensus Committees both defined dyspepsia as pain or discomfort centered in the upper abdomen . Discomfort includes postprandial fullness, upper abdominal bloating, early satiation, epigastric burning, belching, nausea, and vomiting. Heartburn may occur as part of the symptom constellation, but the Rome II Committee decided that when heartburn is the predominant symptom, the patient should be considered to have GERD, not dyspepsia.
The Rome III Consensus Committee, which defined dyspepsia as the presence of symptoms that are considered to originate from the gastroduodenal region , created a major restriction in the definition of dyspepsia, and this was confirmed by the Rome IV Consensus Committee. Only 4 symptoms (postprandial fullness, early satiation, and epigastric pain or epigastric burning) are now considered to be specifically of gastroduodenal origin, although many other symptoms are acknowledged as possibly coexisting.
In patients with dyspepsia, additional clinical investigations may identify underlying organic disease that is likely to cause the symptoms. In these subjects, symptoms are attributable to an organic cause of dyspepsia ( Box 14.1 ). However, in the majority of subjects with dyspeptic symptoms, no organic abnormality is identified by a routine clinical evaluation (including EGD), and these patients are said to have FD . The term uninvestigated dyspepsia refers to dyspeptic symptoms in persons in whom diagnostic investigations have not yet been performed and in whom a specific diagnosis that explains the dyspeptic symptoms has not been determined.
BOX 14.1
Organic Causes of Dyspepsia
Luminal GI Tract
-
Chronic gastric volvulus
-
Chronic gastric or intestinal ischemia
-
Food intolerance
-
Gastric infections (CMV, fungus, tuberculosis, syphilis)
-
Gastric or esophageal neoplasms
-
Gastroesophageal reflux
-
Gastroparesis (diabetes mellitus, postvagotomy, scleroderma, chronic intestinal pseudo-obstruction, postviral, idiopathic)
-
IBS
-
Infiltrative gastric disorders (Ménétrier disease, Crohn disease, eosinophilic gastroenteritis, sarcoidosis, amyloidosis)
-
Parasites (Giardia lamblia, Strongyloides stercoralisrom)
-
PUD
Medications
-
Acarbose
-
Aspirin, other NSAIDs (including COX-2 selective agents)
-
Colchicine
-
Digitalis preparations
-
Estrogens
-
Ethanol
-
Glucocorticoids
-
Iron, potassium chloride
-
Levodopa
-
Narcotics
-
Niacin, gemfibrozil
-
Nitrates
-
Orlistat
-
Quinidine
-
Sildenafil
-
Theophylline
Pancreaticobiliary Disorders
-
Biliary pain: cholelithiasis, choledocholithiasis, SOD
-
Chronic pancreatitis
-
Pancreatic neoplasms
Systemic Conditions
-
Adrenal insufficiency
-
Diabetes mellitus
-
Heart failure
-
Hyperparathyroidism
-
Intra-abdominal malignancy
-
Myocardial ischemia
-
Pregnancy
-
Renal insufficiency
-
Thyroid disease
Organic Causes
The most prevalent identifiable causes underlying dyspeptic symptoms are PUD and GERD. Malignancies of the UGI tract and celiac disease are less common but clinically important organic causes of dyspeptic symptoms (see Box 14.1 ). The investigation of choice in case of dyspeptic symptoms is EGD, which allows identification of erosive esophagitis, Barrett esophagus, peptic ulcer, gastric or duodenal infections, and gastric or esophageal cancer.
Systematic studies indicate that 20% to 25% of patients with dyspeptic symptoms in Western societies have erosive esophagitis, 20% are estimated to have endoscopy-negative reflux disease, 10% have peptic ulcer, 2% have Barrett esophagus, and 1% or less have malignancy. Minor endoscopic or histopathologic findings like duodenitis or gastritis do not seem to correlate with the presence or absence of dyspeptic symptoms.
Intolerance to Food or Drugs
Contrary to popular beliefs, ingestion of specific foods (e.g., spices, coffee, or alcohol) or of excessive amounts of food has never convincingly been established as causing dyspepsia. Although ingestion of food often aggravates dyspeptic symptoms, the effect is probably related to the sensorimotor response to food rather than specific food intolerances or allergies. However, acute ingestion of capsaicin has been shown to induce dyspeptic symptoms in healthy persons and those with FD, with greater intensity in the latter group.
Dyspepsia is a common side effect of many drugs, including iron, antibiotics, narcotics, digitalis, estrogens and oral contraceptives, theophylline, and levodopa. Medications may cause symptoms through direct gastric mucosal injury, changes in GI sensorimotor function, facilitation of gastroesophageal reflux, or idiosyncratic mechanisms. NSAIDs have received the most attention because of their potential to induce ulceration in the GI tract. Chronic use of aspirin and other NSAIDs may provoke dyspeptic symptoms in up to 20% of subjects, but the occurrence of dyspepsia correlates poorly with the presence of an ulcer. In controlled trials, dyspepsia developed in 4% to 8% of persons treated with NSAIDs, with an odds ratios ranging from 1.1 to 3.1 compared with placebo. The magnitude of this effect depends on the dose and type of NSAID. Compared with NSAIDs, COX-2 selective inhibitors are associated with a lower frequency of dyspepsia and peptic ulceration (see Chapter 119 ).
PUD
PUD is a well-established cause of dyspeptic symptoms and is an important consideration for clinicians in the management of these patients. However, the frequency of peptic ulcer in persons with dyspepsia is only 5% to 10%. Increasing age, NSAID use, and Hp infection are the main risk factors for peptic ulcer (see Chapter 53 ).
GERD
Erosive esophagitis is a diagnostic marker for GERD, but most patients with symptoms that are attributable to reflux of stomach contents into the esophagus have no endoscopic signs of esophageal erosion but have so-called nonerosive GERD. Erosive esophagitis is found in approximately 20% of dyspeptic patients, and a similar number of patients may have nonerosive GERD. Empirical use of acid suppressive therapy decreases the likelihood of finding erosive esophagitis in persons with dyspepsia (see Chapter 46 ).
Gastric and Esophageal Cancer
The risk of gastric or esophageal malignancy in patients with dyspeptic symptoms is estimated to be less than 1%. The risk of gastric cancer is increased among persons with Hp infection, a family history of gastric malignancy, or a history of gastric surgery or those who emigrated from areas endemic for gastric malignancy. The risk of esophageal cancer is increased in men, smokers, persons with high alcohol consumption, and those with long-standing heartburn (see Chapter 48, Chapter 54 ).
Biliary and Pancreatic Tract Disorders
Despite the high prevalence of both dyspepsia and gallstones in adults, epidemiologic studies have confirmed that cholelithiasis is not associated with dyspepsia. Therefore, persons with dyspepsia should not be investigated routinely for cholelithiasis, and cholecystectomy in persons with cholelithiasis is not indicated for dyspepsia alone. The clinical presentation of biliary pain is easily distinguishable from that of dyspepsia (see Chapter 65 ).
Pancreatic disease is less prevalent than cholelithiasis, but symptoms of acute or chronic pancreatitis or pancreatic cancer may initially be mistaken for dyspepsia. Pancreatic disorders are usually associated with more severe pain and are often accompanied by anorexia, rapid weight loss, or jaundice (see Chapters 58 to 60 ).
Other GI or Systemic Disorders
Several GI disorders may cause dyspepsia-like symptoms: infectious (e.g., Giardia lamblia and Strongyloides stercoralis infections, tuberculosis, fungal infections, syphilis), inflammatory (celiac disease, Crohn disease, sarcoidosis, lymphocytic gastritis, eosinophilic gastroenteritis), or infiltrative (lymphoma, amyloid, Ménétrier disease) disorders of the UGI tract. Most of these disorders will be identifiable at EGD with mucosal biopsies. Persons with recurrent gastric volvulus and chronic mesenteric or gastric ischemia may also present with dyspeptic symptoms (see Chapters 27 , 30 to 32 , 37 , 107 , 113 , 115 , and 118 ).
The symptom pattern associated with gastroparesis (idiopathic, drug-induced, or secondary to a metabolic, systemic, or neurologic disorder) is similar to dyspepsia, as defined by older definitions. The distinction between idiopathic gastroparesis and FD with delayed gastric emptying is a matter of ongoing debate (see later and Chapter 50 ). Nausea and vomiting are cardinal symptoms in persons with gastroparesis and were not considered symptoms of dyspepsia by the Rome III and Rome IV Consensus Committees, thereby allowing the potential for symptom-based differentiation between dyspepsia and gastroparesis. Dyspepsia may be the presenting or accompanying symptom of acute myocardial ischemia, pregnancy, acute or chronic renal failure, thyroid dysfunction, adrenal insufficiency, and hyperparathyroidism.
Functional Dyspepsia
According to the Rome IV criteria, FD is defined as the presence of early satiation, postprandial fullness, epigastric pain, or epigastric burning in the absence of organic, systemic, or metabolic disease that is likely to explain the symptoms ( Box 14.2 ).
BOX 14.2
Rome IV Criteria for Functional Dyspepsia, Postprandial Distress Syndrome, and Epigastric Pain Syndrome
| Diagnostic criteria ∗ for functional dyspepsia † |
|
| Diagnostic criteria ∗ for postprandial distress syndrome (PDS) | Must include one or both of the following at least 3 days a week:
Supportive Criteria
|
| Diagnostic criteria ∗ for epigastric pain syndrome (EPS) | Must include one or both of the following symptoms at least 1 day a week:
Supportive Criteria
|
∗ Criteria fulfilled for the previous 3 months with symptom onset at least 6 months prior to diagnosis
Dyspepsia Symptom Complex
Pattern and Heterogeneity
The dyspepsia symptom complex is broader than the four cardinal symptoms that constitute the Rome IV definition and includes multiple symptoms such as epigastric pain, early satiation, fullness, epigastric burning, upper abdominal bloating, belching, loss of appetite, nausea, and vomiting. Although often chronic, symptoms in persons with FD are mostly intermittent, even during highly symptomatic episodes. In persons with FD seen in a tertiary care center, the most frequent symptoms are postprandial fullness and bloating, followed by epigastric pain, early satiation, nausea, and belching. There is considerable heterogeneity, however, as demonstrated, for example, in the number of symptoms that patients report ( Fig. 14.1 ). In the general population, the most frequent dyspeptic symptoms are postprandial fullness, early satiation, upper abdominal pain, and nausea.
Weight loss is traditionally considered an “alarm” symptom, pointing toward potentially serious organic disease. Studies in tertiary care patients with FD have also shown a high frequency of unexplained weight loss, and population-based studies in Australia and Europe have shown an association between uninvestigated dyspepsia and unexplained weight loss.
Subgroups
The heterogeneity of the dyspepsia symptom complex is well accepted. Factor analysis of dyspepsia symptoms in the general population and in tertiary care patients with FD have not suggested that FD is a homogeneous (i.e., unidimensional) condition. These studies have confirmed the heterogeneity of the dyspepsia symptom complex but have not provided a clinically meaningful classification of the syndrome.
Several attempts have been made to identify clinically meaningful subgroups of persons with dyspepsia to simplify the intricate heterogeneity of the dyspepsia symptom complex and to guide management. The Rome II Consensus Committee proposed a subdivision based on a predominant symptom of pain or discomfort. Although correlations were found between this classification and the presence or absence of Hp infection, absence or presence of delayed gastric emptying, and response or lack of response to acid suppressive therapy, the classification has been criticized because of the difficulty in distinguishing pain from discomfort, lack of a widely accepted definition of “predominant,” uncertainty about overlap between the symptom subgroups, absence of an association with putative pathophysiologic mechanisms, and, especially, lack of stability of the predominant symptom over short time periods.
The Rome III Consensus Committee proposed a different classification ( Fig. 14.2 ). Studies in patients with FD seen at a tertiary care center and persons with uninvestigated dyspepsia in the general population have revealed that between 40% and 75% of dyspeptic persons report aggravation of symptoms after ingestion of a meal. Assuming that a distinction between meal-related and meal-unrelated symptoms might be pathophysiologically and clinically relevant, the Rome III Consensus Committee proposed that FD be considered an umbrella term and that the postprandial distress syndrome (PDS)—characterized by meal-related dyspeptic symptoms, postprandial fullness, and early satiation be distinguished from the epigastric pain syndrome (EPS)—characterized by meal-unrelated dyspeptic symptoms, epigastric pain, and epigastric burning. In population-based studies, the Rome III–based classification of FD into EPS and PDS showed the existence of both entities, with little overlap between them. By contrast, studies of persons with FD who sought consultation with a physician have shown major overlap in Rome III–defined PDS and EPS. The Rome IV Consensus Committee aimed to reduce this overlap by considering all postprandially occurring symptoms to be part of the PDS. Therefore, when epigastric pain occurs postprandially in patients with early satiation or postprandial fullness, the patient is still categorized as having the PDS (see Fig. 14.2 ). Epidemiologic studies and studies in patient cohorts have shown that the PDS is the dominant subgroup and that overlap with the EPS is small with the Rome IV classification.
Overlap with Heartburn and IBS
The issue of overlap between dyspepsia and GERD has been a challenging one. Although earlier investigators considered a group of patients with reflux-like dyspepsia, the Rome Consensus Committees did not consider heartburn to arise primarily from the gastroduodenal region, and this symptom was excluded from the definition of dyspepsia. Heartburn commonly coexists with dyspepsia, however, in both the general population and patients with FD. Moreover, distinguishing GERD from dyspepsia is hampered by a number of confounding factors, such as the presence of dyspepsia-type symptoms in many patients with GERD and difficulties in recognizing heartburn by patients and physicians.
The Rome II Consensus Committee stated that patients with typical heartburn as a dominant complaint almost invariably have GERD and should be distinguished from patients with dyspepsia. Although this distinction is valid, the Rome III Consensus Committee proposed identifying patients with frequent heartburn and using a word-picture questionnaire to identify patients with FD who will respond to acid-suppressive therapy or in whom pathologic esophageal acid exposure can be demonstrated. The Rome III and IV Consensus Committees state that heartburn is not a gastroduodenal symptom, although it often occurs in association with symptoms of FD and its presence does not exclude a diagnosis of FD. Similarly, the frequent co-occurrence of FD and IBS is explicitly recognized in the Rome III and IV consensus guidelines and does not exclude a diagnosis of FD.
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