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American Gastroenterological Association Technical Review on the Evaluation of Dyspepsia

2005; Elsevier BV; Volume: 129; Issue: 5 Linguagem: Inglês

10.1053/j.gastro.2005.09.020

1528-0012

Nicholas J. Talley, Nimish Vakil, Paul Moayyedi,

Gastroesophageal reflux and treatments

This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Economics Committee. The paper was approved by the Committee on April 22, 2005, and by the AGA Governing Board on October 6, 2005. This literature review and the recommendations therein were prepared for the American Gastroenterological Association Clinical Practice and Economics Committee. The paper was approved by the Committee on April 22, 2005, and by the AGA Governing Board on October 6, 2005. Since the publication of the initial technical review on evaluation of dyspepsia in 1998,1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar test and treat for Helicobacter pylori has become very widely accepted as the approach of choice in those with chronic dyspepsia but no alarm features.2Talley N.J. Axon A.T. Bytzer P. Holtmann G. Lam S.K. Van Zanten S.J. Management of uninvestigated and functional dyspepsia a Working Party report for the World Congresses of Gastroenterology 1998.Aliment Pharmacol Ther. 1999; 13: 1135-1148Crossref PubMed Scopus (93) Google Scholar, 3Tytgat G.N. Hungin A. Malfertheiner P. Talley N.J. Hongo M. McColl K. Soule J.C. Agreus L. Bianchi-Porro G. Freston J. Hunt R. Decision-making in dyspepsia controversies in primary and secondary care.Eur J Gastroenterol Hepatol. 1999; 11: 223-230Crossref PubMed Google Scholar, 4Veldhuyzen van Zanten S. Flook N. Chiba N. Armstrong D. Barkun A. Bradette M. Thomson A. Bursey F. Blackshaw P.E. Frail D. Sinclair P. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori.CMAJ. 2000; 162: S3-S23PubMed Google Scholar, 5Talley N.J. Lam S.K. Goh K.L. Fock K.M. Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region First Asian Pacific Working Party on Functional Dyspepsia.J Gastroenterol Hepatol. 1998; 13: 335-353Crossref PubMed Google Scholar, 6Talley N.J. Vakil N. Delaney B. Marshall B. Bytzer P. Engstrand L. de Boer W. Jones R. Malfertheiner P. Agreus L. Management issues in dyspepsia current consensus and controversies.Scand J Gastroenterol. 2004; 39: 913-918Crossref PubMed Scopus (18) Google Scholar However, this choice was based predominantly on the results of decision analyses, because limited management trial evidence was available 7 years ago. Indeed, in primary care, empirical antisecretory therapy continues to be often prescribed, but whether this is the most cost-effective and safest approach remains debated.7Health and Public Policy CommitteeEndoscopy in the evaluation of dyspepsia.Ann Intern Med. 1985; 102: 266-269Crossref PubMed Google Scholar, 8Chiba N. Treat the patients' main dyspepsia complaint, not the ROME criteria.Am J Gastroenterol. 2004; 99: 1059-1062Crossref PubMed Scopus (12) Google Scholar, 9Talley N.J. Dyspepsia management in the millennium the death of test and treat?.Gastroenterology. 2002; 122: 1521-1525Abstract Full Text Full Text PDF PubMed Google Scholar Further, gastroenterologists often still elect to undertake prompt esophagogastroduodenoscopy (EGD) in all cases to reassure both patient and physician and treat specific disease (eg, peptic ulcer, esophagitis, Barrett's esophagus, or malignancy) rather than rely on any kind of empirical approach.9Talley N.J. Dyspepsia management in the millennium the death of test and treat?.Gastroenterology. 2002; 122: 1521-1525Abstract Full Text Full Text PDF PubMed Google Scholar However, it is known that the prevalence of H pylori infection has continued to dramatically decline, as has the identification of peptic ulcer disease and gastric (but not cardia or esophageal) adenocarcinoma at EGD.9Talley N.J. Dyspepsia management in the millennium the death of test and treat?.Gastroenterology. 2002; 122: 1521-1525Abstract Full Text Full Text PDF PubMed Google Scholar Moreover, the prevalence of H pylori infection varies widely across the United States and is different by age and race.10Everhart J.E. Kruszon-Moran D. Perez-Perez G.I. Tralka T.S. McQuillan G. Seroprevalence and ethnic differences in Helicobacter pylori infection among adults in the United States.J Infect Dis. 2000; 181: 1359-1363Crossref PubMed Scopus (170) Google Scholar The use of cyclooxygenase-2–selective nonsteroidal anti-inflammatory drugs (NSAIDs) was common but has declined whereas prophylactic use of low-dose aspirin is increasing, also variably affecting ulcer rates.11Hawkey C.J. Langman M.J. Non-steroidal anti-inflammatory drugs: overall risks and management. Complementary roles for COX-2 inhibitors and proton pump inhibitors.Gut. 2003; 52: 600-608Crossref PubMed Scopus (118) Google Scholar, 12Feldman M. McMahon A.T. Do cyclooxygenase-2 inhibitors provide benefits similar to those of traditional nonsteroidal anti-inflammatory drugs, with less gastrointestinal toxicity?.Ann Intern Med. 2000; 132: 134-143Crossref PubMed Google Scholar On the other hand, the prevalence of esophagitis detected at EGD may be increasing despite more rigorous and reliable classification (eg, the LA classification) for the presence of this condition.13Thomson A. Barkun A. Armstrong D. Chiba N. White R. Daniel S. Escobedo S. Chakraborty B. Sinclair P. vanZanten S. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia the Canadian Adult Dyspepsia Empiric treatment-prompt endoscopy (CADET-PE) study.Aliment Pharmacol Ther. 2003; 17: 1481-1491Crossref PubMed Scopus (198) Google Scholar Over-the-counter H2 blockers and proton pump inhibitors (PPIs) mean that many patients end up on antisecretory therapy first anyway, regardless of what physicians recommend,14Jacobson B.C. Ferris T.G. Shea T.L. Mahlis E.M. Lee T.H. Wang T.C. Who is using chronic acid suppression therapy and why?.Am J Gastroenterol. 2003; 98: 51-58Crossref PubMed Scopus (70) Google Scholar and their use may impair the ability of EGD to detect esophagitis or peptic ulceration.Our aim was to review all the available management strategies in the literature and critically evaluate them to help develop practice recommendations for dyspepsia and functional (nonulcer) dyspepsia. To do this, MEDLINE and Current Contents searches were performed from April 1997 (the date of completion of the previous report) to July 2004 using the Medical Subject Heading (MeSH) terms dyspepsia, nonulcer dyspepsia, functional dyspepsia, and H pylori. In addition, specific searches were performed with the support of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group, and these will be highlighted in the appropriate sections. The reports that considered management of dyspepsia and functional dyspepsia were retrieved and reviewed, and their reference lists were checked for additional citations. The authors met to review the available data in order to produce currently applicable recommendations for the United States.DefinitionsThe definition of dyspepsia remains controversial.15Westbrook J.I. McIntosh J.H. Talley N.J. The impact of dyspepsia definition on prevalence estimates considerations for future researchers.Scand J Gastroenterol. 2000; 3: 227-233Google Scholar Guidelines from the United Kingdom16Dyspepsia. National Institute of Clinical Excellence, London, England2004Google Scholar and Canada4Veldhuyzen van Zanten S. Flook N. Chiba N. Armstrong D. Barkun A. Bradette M. Thomson A. Bursey F. Blackshaw P.E. Frail D. Sinclair P. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori.CMAJ. 2000; 162: S3-S23PubMed Google Scholar use the term to mean all (or almost all) symptoms referable to the upper gastrointestinal tract, whereas the Rome II definition17Talley N.J. Stanghellini V. Heading R.C. Koch K.L. Malagelada J. Tytgat G.N. Functional gastroduodenal disorders.in: Drossman D.A. Rome II the functional gastrointestinal disorders. Degnon, McLean, VA2000: 299-350Google Scholar excludes patients with predominant reflux symptoms. The rationale for the Rome II definition is that when classic heartburn or regurgitation are the only or predominant symptoms or occur frequently (more than once a week), objective evidence of gastroesophageal reflux disease (GERD) can often be identified. The problem is that there is no gold standard for diagnosing GERD; patients often find it difficult to describe a predominant symptom, and even when this is possible, the predominant symptom may change over time.18Moayyedi P. Duffy J. Delaney B. New approaches to enhance the accuracy of the diagnosis of reflux disease.Gut. 2004; 53: 55-57Google Scholar Furthermore, in clinical practice, there is considerable overlap among reflux and dyspeptic symptoms; in a Canadian study in primary care, the mean number of symptoms reported in patients labeled broadly as having dyspepsia was 6 and often included typical heartburn.13Thomson A. Barkun A. Armstrong D. Chiba N. White R. Daniel S. Escobedo S. Chakraborty B. Sinclair P. vanZanten S. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia the Canadian Adult Dyspepsia Empiric treatment-prompt endoscopy (CADET-PE) study.Aliment Pharmacol Ther. 2003; 17: 1481-1491Crossref PubMed Scopus (198) Google Scholar It is therefore difficult to establish the accuracy of predominant reflux symptoms for diagnosing GERD in the uninvestigated patient in primary care.Despite these caveats, this review will follow the Rome II definition and the term "dyspepsia" here will be restricted to mean chronic or recurrent pain or discomfort centered in the upper abdomen (ie, the epigastrium); symptoms of reflux as defined above and acute abdominal conditions will not be included.17Talley N.J. Stanghellini V. Heading R.C. Koch K.L. Malagelada J. Tytgat G.N. Functional gastroduodenal disorders.in: Drossman D.A. Rome II the functional gastrointestinal disorders. Degnon, McLean, VA2000: 299-350Google Scholar We have taken this view because the Rome II criteria or modified criteria have been and continue to be most widely used in large randomized controlled trials of new drugs for functional dyspepsia.19Moayyedi P. Soo S. Deeks J. Delaney B. Harris A. Innes M. Oakes R. Wilson S. Roalfe A. Bennett C. Forman D. Eradication of Helicobacter pylori for non-ulcer dyspepsia.Cochrane Database Syst Rev. 2003; 1: CD002096PubMed Google Scholar, 20Moayyedi P. Delaney B. Vakil N. Forman D. Talley N. The efficacy of proton pump inhibitors in non-ulcer dyspepsia a systematic review and economic analysis.Gastroenterology. 2004; 127: 1329-1337Abstract Full Text Full Text PDF PubMed Scopus (140) Google Scholar There are data that heartburn often overlaps with epigastric pain13Thomson A. Barkun A. Armstrong D. Chiba N. White R. Daniel S. Escobedo S. Chakraborty B. Sinclair P. vanZanten S. The prevalence of clinically significant endoscopic findings in primary care patients with uninvestigated dyspepsia the Canadian Adult Dyspepsia Empiric treatment-prompt endoscopy (CADET-PE) study.Aliment Pharmacol Ther. 2003; 17: 1481-1491Crossref PubMed Scopus (198) Google Scholar; however, based on expert opinion, where symptoms of reflux are prominent, GERD should be the diagnosis until proven otherwise in gastroenterology practice.Because meal-related symptoms are not discriminating, the relationship to meals has not been considered part of the definition, although it is likely that a large subset will have meal-related complaints.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 21Talley N.J. Weaver A.L. Tesmer D.L. Zinsmeister A.R. Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.Gastroenterology. 1993; 105: 1378-1386Abstract Full Text PDF PubMed Google Scholar, 22Talley N.J. McNeil D. Piper D.W. Discriminant value of dyspeptic symptoms a study of the clinical presentation of 221 patients with dyspepsia of unknown cause, peptic ulceration, and cholelithiasis.Gut. 1987; 28: 40-46Crossref PubMed Google Scholar, 23Feinle-Bisset C. Vozzo R. Horowitz M. Talley N.J. Diet, food intake, and disturbed physiology in the pathogenesis of symptoms in functional dyspepsia.Am J Gastroenterol. 2004; 99: 170-181Crossref PubMed Scopus (72) Google Scholar It has been proposed that weight loss is a specific symptom of dyspepsia associated with early satiety and reduced oral intake, but this is controversial.24Tack J. Piessevaux H. Coulie B. Caenepeel P. Janssens J. Role of impaired gastric accommodation to a meal in functional dyspepsia.Gastroenterology. 1998; 115: 1346-1352Abstract Full Text Full Text PDF PubMed Google Scholar, 25Bredenoord A.J. Chial H.J. Camilleri M. Mullan B.P. Murray J.A. Gastric accommodation and emptying in evaluation of patients with upper gastrointestinal symptoms.Clin Gastroenterol Hepatol. 2003; 1: 264-272Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Bloating is difficult to localize to a specific abdominal site and is more typically a symptom of irritable bowel syndrome (IBS),26Zar S. Benson M.J. Kumar D. Review article bloating in functional bowel disorders.Aliment Pharmacol Ther. 2002; 16: 1867-1876Crossref PubMed Scopus (18) Google Scholar so it may be best not to consider this a characteristic feature of dyspepsia. It has been suggested that if the upper abdominal pain or discomfort is relieved by defecation or associated with altered stool symptoms, the diagnosis of IBS should be strongly entertained,17Talley N.J. Stanghellini V. Heading R.C. Koch K.L. Malagelada J. Tytgat G.N. Functional gastroduodenal disorders.in: Drossman D.A. Rome II the functional gastrointestinal disorders. Degnon, McLean, VA2000: 299-350Google Scholar but the importance of this distinction is not established. Nausea can be due to gastric, intestinal, or extraintestinal causes; alone it is not sufficient to identify dyspepsia, although it may cluster with these symptoms.27Eslick G.D. Howell S.C. Hammer J. Talley N.J. Empirically derived symptom sub-groups correspond poorly with diagnostic criteria for functional dyspepsia and irritable bowel syndrome A factor and cluster analysis of a patient sample.Aliment Pharmacol Ther. 2004; 19: 133-140Crossref PubMed Scopus (29) Google Scholar Recurrent belching is common but is most often attributable to air swallowing28Quigley E.M.M. From comic relief to real understanding; how intestinal gas causes symptoms.Gut. 2003; 52: 1659-1661Crossref PubMed Scopus (19) Google Scholar and alone is not considered to constitute dyspepsia in the absence of upper abdominal discomfort.It is assumed here when identifying dyspepsia that the physician evaluating the patient, after the history and physical examination, considers the symptoms to probably arise from the upper gastrointestinal tract and not from the abdominal wall muscles, chest, or elsewhere.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar The Rome committees have previously endorsed similar criteria.17Talley N.J. Stanghellini V. Heading R.C. Koch K.L. Malagelada J. Tytgat G.N. Functional gastroduodenal disorders.in: Drossman D.A. Rome II the functional gastrointestinal disorders. Degnon, McLean, VA2000: 299-350Google Scholar "Uninvestigated dyspepsia" refers here to patients with symptoms of dyspepsia who have not undergone testing to exclude peptic ulcer disease or upper gastrointestinal malignancy. "Investigated dyspepsia" is used to describe patients who have had a relevant structural evaluation. "Functional dyspepsia" is a clinical syndrome; no evidence of peptic ulcer, upper gastrointestinal malignancy, or GERD has been found by definition on routine testing.Scope of the ReviewReflux symptoms and epigastric pain are both treated with acid suppression and investigated with endoscopy; as noted previously, there is often overlap among symptoms. The review will focus on patients presenting with predominant epigastric pain or discomfort and will not assess the management of GERD.29DeVault K.R. Castell D.O. Updated guildelines for the diagnosis and treatment of gastroesophageal reflux disease.Am J Gastroenterol. 2005; 100: 190-200Crossref PubMed Scopus (500) Google Scholar The optimum management of Barrett's esophagus is also not addressed for similar reasons.30Sampliner R.E. Practice Parameters Committee of the American College of GastroenterologyUpdated guidelines for the diagnosis, surveillance, and therapy of Barrett's esophagus.Am J Gastroenterol. 2002; 97: 1888-1895Crossref PubMed Google Scholar, 31Management of Barrett's esophagusThe Society for Surgery of the Alimentary Tract (SSAT), American Gastroenterological Association (AGA), American Society for Gastrointestinal Endoscopy (ASGE) Consensus Panel.J Gastrointest Surg. 2000; 4: 115-116Crossref PubMed Google ScholarThe management of dyspepsia related to NSAIDs, including aspirin, is a significant problem. The appropriate management of the risk of peptic ulcer complications associated with long-term use of NSAIDs is also an important issue, but this is beyond the scope of this document.32Goldstein J.L. Challenges in managing NSAID-associated gastrointestinal tract injury.Digestion. 2004; 69: 25-33Crossref PubMed Scopus (25) Google Scholar, 33Hunt R.H. Bazzoli F. Should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing.Aliment Pharmacol Ther. 2004; 19: 9-16Crossref PubMed Google Scholar, 34Rostom A. Dube C. Wells G. Tugwell P. Welch V. Jolicoeur E. McGowan J. Prevention of NSAID-induced gastroduodenal ulcers.Cochrane Database Syst Rev. 2002; 4: CD002296PubMed Google ScholarEpidemiologyThe annual prevalence of recurrent upper abdominal pain or discomfort in the United States and other Western countries is approximately 25%; if frequent heartburn (defined as rising retrosternal burning pain or discomfort weekly or more often) is also considered, the prevalence approaches 40%.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 35El-Serag H.B. Talley N.J. Systematic review the prevalence and clinical course of functional dyspepsia.Aliment Pharmacol Ther. 2004; 19: 643-654Crossref PubMed Scopus (170) Google Scholar The incidence of dyspepsia (number of new disease cases per population at risk) is poorly documented; however, in Scandinavia over a 3-month period, dyspepsia developed in <1%.36Agreus L. Svardsudd K. Nyren O. Tibblin G. Irritable bowel syndrome and dyspepsia in the general population overlap and lack of stability over time.Gastroenterology. 1995; 109: 671-680Abstract Full Text PDF PubMed Scopus (531) Google Scholar Notably, the number of subjects who develop dyspepsia appears to be matched by a similar number of subjects who lose their symptoms, so the prevalence remains stable from year to year.37Agreus L. Svardsudd K. Talley N.J. Jones M.P. Tibblin G. Natural history of gastroesophageal reflux disease and functional abdominal disorders a population-based study.Am J Gastroenterol. 2001; 96: 2905-2914Crossref PubMed Scopus (169) Google Scholar, 38Talley N. Weaver A. Zinsmeister A. Melton III, L.J. Onset and disappearance of gastrointestinal symptoms and functional gastrointestinal disorders.Am J Epidemiol. 1992; 136: 165-177PubMed Google Scholar The pattern of individual symptom cycling in dyspepsia has not yet been adequately documented, but symptom relapse is probably the rule.Definitions of dyspepsia also impact on the prevalence.15Westbrook J.I. McIntosh J.H. Talley N.J. The impact of dyspepsia definition on prevalence estimates considerations for future researchers.Scand J Gastroenterol. 2000; 3: 227-233Google Scholar For example, in the US householder study of volunteers, the prevalence of dyspepsia was 13%; one third of the population had heartburn.39Drossman D. Li Z. Andruzzi E. Temple R. Talley N. Thompson W. Whitehead W. Janssens J. Funch-Jensen P. Corazziari E. U.S. householder survey of functional gastrointestinal disorders Prevalence, sociodemography, and health impact.Dig Dis Sci. 1993; 38: 1569-1580Crossref PubMed Scopus (1404) Google Scholar However, if heartburn and symptoms of IBS were excluded from the dyspepsia category, only 3% of the population still had a diagnosis of dyspepsia.39Drossman D. Li Z. Andruzzi E. Temple R. Talley N. Thompson W. Whitehead W. Janssens J. Funch-Jensen P. Corazziari E. U.S. householder survey of functional gastrointestinal disorders Prevalence, sociodemography, and health impact.Dig Dis Sci. 1993; 38: 1569-1580Crossref PubMed Scopus (1404) Google ScholarDyspepsia remains a costly, chronic condition, and drug costs in particular continue to increase rapidly.40Henke C.J. Levin T.R. Henning J.M. Potter L.P. Work loss costs due to peptic ulcer disease and gastroesophageal reflux disease in a health maintenance organization.Am J Gastroenterol. 2000; 95: 788-792Crossref PubMed Google Scholar, 41Kurata J.H. Nogawa A.N. Everhart J.E. A prospective study of dyspepsia in primary care.Dig Dis Sci. 2002; 47: 797-803Crossref PubMed Scopus (12) Google Scholar In many cases, the symptoms are of short duration or mild severity and are self-managed.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 42Shi C.W. Gralnek I.M. Dulai G.S. Towfigh A. Asch S. Consumer usage patterns of nonprescription histamine2-receptor antagonists.Am J Gastroenterol. 2004; 99: 606-610Crossref PubMed Scopus (12) Google Scholar, 43Shaw M.J. Fendrick A.M. Kane R.L. Adlis S.A. Talley N.J. Self-reported effectiveness and physician consultation rate in users of over-the-counter histamine-2 receptor antagonists.Am J Gastroenterol. 2001; 96: 673-676Crossref PubMed Google Scholar Less than half in the United States and Europe seek medical care for their dyspepsia.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 35El-Serag H.B. Talley N.J. Systematic review the prevalence and clinical course of functional dyspepsia.Aliment Pharmacol Ther. 2004; 19: 643-654Crossref PubMed Scopus (170) Google Scholar, 44Talley N.J. Zinsmeister A.R. Schleck C.D. Melton III, L.J. Dyspepsia and dyspepsia subgroups a population-based study.Gastroenterology. 1992; 102: 1259-1268PubMed Google Scholar Even so, the management of dyspepsia represents a major component of clinical practice; 2%–5% of family practice consultations are for dyspepsia.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 45Majumdar S.R. Soumerai S.B. Farraye F.A. Lee M. Kemp J.A. Henning J.M. Schrammel P. LeCates R.F. Ross-Degnan D. Chronic acid-related disorders are common and underinvestigated.Am J Gastroenterol. 2003; 98: 2409-2414Crossref PubMed Scopus (33) Google Scholar The factors that determine whether a patient consults a physician may include symptom severity, older age, lower social class, fear of serious disease, psychological comorbidity and insurance status.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 46Koloski N. Talley N. Boyce P. Predictors of health care seeking for irritable bowel syndrome and nonulcer dyspepsia a critical review of the literature on symptom and psychosocial factors.Am J Gastroenterol. 2001; 96: 1340-1349Crossref PubMed Google Scholar, 47Koloski N.A. Talley N.J. Huskic S.S. Boyce P.M. Predictors of conventional and alternative health care seeking for irritable bowel syndrome and functional dyspepsia.Aliment Pharmacol Ther. 2003; 17: 841-851Crossref PubMed Scopus (78) Google Scholar, 48Talley N.J. Boyce P. Jones M. Dyspepsia and health care seeking in a community how important are psychological factors?.Dig Dis Sci. 1998; 43: 1016-1022Crossref PubMed Scopus (68) Google Scholar, 49Howell S. Talley N.J. Does fear of serious disease predict consulting behaviour amongst patients with dyspepsia in general practice?.Eur J Gastroenterol Hepatol. 1999; 11: 881-886Crossref PubMed Google Scholar Functional dyspepsia impacts negatively on quality of life.50El-Serag H.B. Talley N.J. Systematic review health-related quality of life in functional dyspepsia.Aliment Pharmacol Ther. 2003; 18: 387-393Crossref PubMed Scopus (72) Google Scholar Here, attention will be focused on the management of those individuals with dyspepsia who seek medical attention (consulters) rather than on people with dyspepsia in the general community who do not seek medical care.Differential Diagnosis of DyspepsiaPatients presenting with predominant epigastric pain or discomfort who have not undergone any investigations are defined as having uninvestigated dyspepsia. Those patients with an obvious source such as abdominal wall pain are not considered to have dyspepsia. In patients with dyspepsia who are investigated, there are 4 major causes: chronic peptic ulcer disease, gastroesophageal reflux (with or without esophagitis), malignancy, and functional (or nonulcer) dyspepsia. The latter remains essentially a diagnosis of exclusion.Structural AbnormalitiesA number of studies have reported the prevalence of endoscopic findings in patients with dyspeptic symptoms in primary care and gastroenterology practices.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar Many of these studies were performed before knowledge of H pylori infection and its treatment and before antisecretory drugs became widely available. Therefore, these studies have limited utility in today's practice. Recent studies suggest that the prevalence of underlying abnormalities in unselected dyspeptic patients undergoing endoscopy may depend to some extent on the definition of dyspepsia and the prevalence of H pylori infection and GERD in the underlying population.35El-Serag H.B. Talley N.J. Systematic review the prevalence and clinical course of functional dyspepsia.Aliment Pharmacol Ther. 2004; 19: 643-654Crossref PubMed Scopus (170) Google ScholarA peptic ulcer is found in approximately 5%–15% of patients with dyspepsia in North America.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 4Veldhuyzen van Zanten S. Flook N. Chiba N. Armstrong D. Barkun A. Bradette M. Thomson A. Bursey F. Blackshaw P.E. Frail D. Sinclair P. An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori.CMAJ. 2000; 162: S3-S23PubMed Google Scholar An ulcer, however, may be missed if the patient is already on empirical antisecretory therapy (a common scenario and aggravated by the availability of over-the-counter PPIs in the United States). A chronic duodenal ulcer is usually caused by H pylori (up to 90% of patients are infected, but this varies geographically); chronic gastric ulcer commonly results from H pylori (approximately 70% of cases) or use of nonselective NSAIDs, including low-dose aspirin.1Talley N.J. Silverstein M.D. Agréus L. Nyrén O. Sonnenberg A. Holtmann G. AGA technical review evaluation of dyspepsia.Gastroenterology. 1998; 114: 582-595Abstract Full Text Full Text PDF PubMed Scopus (361) Google Scholar, 51Soll A.H. Consensus conference. Medical treatment of peptic ulcer disease: practice guidelines. Practice Parameters of the American College of Gastroenterology.JAMA. 1996; 275: 622-629Crossref PubMed Google Scholar Individual dyspeptic symptoms cannot be used to help identify peptic ulcer disease in uninvestigated dyspepsia.21Talley N.J. Weaver A.L. Tesmer D.L. Zinsmeister A.R. Lack of discriminant value of dyspepsia subgroups in patients referred for upper endoscopy.Gastroenterology. 1993; 105: 1378-1386Abstract Full Text PDF PubMed Google Scholar, 22Talley N.J. McNeil D. Piper D.W. Discriminant value of dyspeptic symptoms a study of the clinical presentation of 221 patients with dyspepsia of unknown cause, peptic ulceration, and cholelithiasis.Gut. 1987; 28: 40-46Crossref PubMed Google Scholar Experts have suggested that subdividing dyspepsia into subgroups based on symptom patterns might help identify underlying structural disease as well as more homogeneous populations that would respond to targeted medical therapy.17Talley N.J. Stanghellini V. Heading R.C. Koch K.L. Malagelada J. Tytgat G.N. Functional gastroduodenal disorders.in: Drossman D.A. Rome II the functional gastrointestinal disorders. Degnon, McLean, VA2000: 299-350Google Scholar However, symptom subgroups and symptom scori