Dyspepsia refers to acute, chronic, or recurrent pain or discomfort centered in the upper abdomen. An international committee of clinical investigators (Rome III Committee) has defined dyspepsia as epigastric pain or burning, early satiety, or postprandial fullness. Heartburn (retrosternal burning) should be distinguished from dyspepsia. When heartburn is the dominant complaint, gastroesophageal reflux is nearly always present. Dyspepsia occurs in 15% of the adult population and accounts for 3% of general medical office visits.
▶ Symptoms and Signs
The discomfort may be characterized by one or more upper abdominal symptoms including epigastric pain or burning, early satiety, postprandial fullness, bloating, nausea, or vomiting. Concomitant weight loss, persistent vomiting, constant or severe pain, dysphagia, hematemesis, or melena warrants endoscopy or abdominal imaging.
Potentially offending medications and excessive alcohol use should be identified and discontinued if possible. The patient’s reason for seeking care should be determined. Recent changes in employment, marital discord, physical and sexual abuse, anxiety, depression, and fear of serious disease may all contribute to the development and reporting of symptoms. Patients with functional dyspepsia often are younger, report a variety of abdominal and extra gastrointestinal complaints, show signs of anxiety or depression, or have a history of use of psychotropic medications.
The symptom profile alone does not differentiate between functional dyspepsia and organic gastrointestinal disorders. Based on the clinical history alone, primary care clinicians misdiagnose nearly half of patients with peptic ulcers or gastroesophageal reflux and have < 25% accuracy in diagnosing functional dyspepsia. The physical examination is rarely helpful. Signs of serious organic disease such as weight loss, organomegaly, abdominal mass, or fecal occult blood are to be further evaluated.
Helicobacter pylori Infection
The role of H pylori in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between H pylori infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status. Controlled trials disagree about whether or not H pylori eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement.In a recent multicenter U.S.trial that randomized 240 patients to treatment or placebo, and followed patients for 12 months, 28% of treated patients versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after H pylori eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results.A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89;P= 0.18).Still,no effect was seen after adjusting for heterogeneity and for cure of H pylori. In contrast, the most recent update of a Cochrane Database review showed a small but statistically significant effect in curing symptoms.
in patients older than age of 55 years, initial laboratory work should include a blood count, electrolytes, liver enzymes, calcium, and thyroid function tests. In patients younger than 55 years with uncomplicated dyspepsia (in whom gastric cancer is rare), initial noninvasive strategies should be pursued (see below). The cost-effectiveness of routine laboratory studies is uncertain. In most clinical settings, a noninvasive test for H pylori (urea breath test, fecal antigen test, or IgG serology) should be performed first. Although serologic tests are inexpensive, performance characteristics are poor in low-prevalence populations, whereas breath and fecal antigen tests have 95% accuracy. If H pylori breath test or fecal antigen test results are negative in a patient not taking NSAIDs, peptic ulcer disease is virtually excluded.
Upper endoscopy is indicated to look for gastric cancer or other serious organic disease in all patients over age 55 years with new-onset dyspepsia and in all patients with “alarm” features, such as weight loss, dysphagia, recurrent vomiting, evidence of bleeding, or anemia. Upper endoscopy is the study of choice to diagnose gastroduodenal ulcers, erosive esophagitis, and upper gastrointestinal malignancy. It is also helpful for patients who are concerned about serious underlying disease. For patients born in regions in which there is a higher incidence of gastric cancer, such as Central or South America, China and Southeast Asia, or Africa, an age threshold of 45 years may be appropriate.
Endoscopic evaluation is also warranted when symptoms fail to respond to initial empiric management strategies within 4–8 weeks or when frequent symptom relapse occurs after discontinuation of antisecretory therapy.
In patients with refractory symptoms or progressive weight loss, antibodies for celiac disease or stool testing for ova and parasites or Giardia antigen, fat, or elastase may be considered. Abdominal imaging (ultrasonography or CT scanning) is performed only when pancreatic, biliary tract, vascular disease, or volvulus is suspected. Gastric emptying studies are valuable only in patients with recurrent vomiting. Ambulatory esophageal pH testing may be of value when atypical gastroesophageal reflux is suspected.
Initial empiric treatment is warranted for patients who are < 55 years and who have no alarm features (defined above). All other patients as well as patients whose symptoms fail to respond or relapse after empiric treatment should undergo upper endoscopy with subsequent treatment directed at the specific disorder (eg, peptic ulcer, gastroesophageal reflux, cancer). Most patients will have no significant findings on endoscopy and will be given a diagnosis of functional dyspepsia.
Young patients with uncomplicated dyspepsia may be treated empirically with either a proton pump inhibitor or evaluated with a noninvasive test for H pylori, followed if positive by treatment. The prevalence of H pylori in the population influences recommendations for the timing of these empiric therapies. In clinical settings in which the prevalence of H pylori infection in the population is low (< 10%), it may be more cost-effective to initially treat patients with a 4-week trial of a proton pump inhibitor. Patients who have symptom relapse after discontinuation of the proton pump inhibitor should be tested for H pylori and treated if results are positive. In clinical settings in which H pylori prevalence is >10%, it may be more costeffective to initially test patients for H pylori infection. H pylori–negative patients most likely have functional dyspepsia or atypical GERD and can be treated with an antisecretory agent (proton pump inhibitor) for 4 weeks. For patients who have symptom relapse after discontinuation of the proton pump inhibitor, intermittent or longterm proton pump inhibitor therapy may be considered. For patients in whom test results are positive for H pylori, antibiotic therapy proves definitive for patients with underlying peptic ulcers and may improve symptoms in a small subset (< 10%) of infected patients with functional dyspepsia. Patients with persistent dyspepsia after H pylori eradication can be given a trial of proton pump inhibitor therapy.
Ford AC et al. Dyspepsia. BMJ. 2013 Aug 29;347:f50509. [PMID: 23990632]
Mazzoleni LE et al. Helicobacter pylori eradication in functional dyspepsia: HEROES trial. Arch Intern Med. 2011 Nov 28;171(21):1929–36. [PMID: 22123802] Zhao B et al. Efficacy of Helicobacter pylori eradication therapy on functional dyspepsia: a meta-analysis of randomized controlled studies with 12-month follow-up. J Clin Gastroenterol. 2014 Mar;48(3):241–7. [PMID: 24002127]
Laine L, Schoenfeld P, Fennerty MB. Therapy for Helicobacter pylori in patients with nonulcer dyspepsia. A meta-analysis of randomized, controlled trials. Ann Intern Med. 2001;134: 361–369. [PMID: 11242496] Moayyedi P, Deeks J, Talley NJ, et al. An update of the Cochrane systematic review of Helicobacter pylori eradication therapy in nonulcer dyspepsia: resolving the discrepancy between systematic reviews. Am J Gastroenterol. 2003;98:2621–2626. [PMID: 14687807] Talley NJ,Quan C.Review article: Helicobacter pylori and nonulcer dyspepsia. Aliment Pharmacol Ther. 2002;16(Suppl 1):58–65. [PMID: 11849130]