Evaluation of dyspepsia

Dyspepsia is a symptom or a combination of symptoms that alerts a clinician to the presence of an upper gastrointestinal (UGI) problem. Typical symptoms include epigastric pain or burning, early satiety and postprandial fullness, belching, bloating, nausea, or discomfort in the upper abdomen. Symptoms are the central focus of this assessment; it is therefore essential that they are described in a manner that is relevant to patients.[1]Vakil NB, Halling K, Becher A, et al. Systematic review of patient-reported outcome instruments for gastroesophageal reflux disease symptoms. Eur J Gastroenterol Hepatol. 2013 Jan;25(1):2-14. http://www.ncbi.nlm.nih.gov/pubmed/23202695?tool=bestpractice.com

Clinicians using symptom-based assessment of UGI symptoms need to be aware of the diagnostic uncertainty inherent in this approach. These assessments can provide functional working diagnoses, but there is always a danger of misclassification. An important consequence of the inability to make a definitive diagnosis based on symptoms alone is an over-diagnosis of GERD and the under-recognition of Helicobacter pylori-related disease. Periodic reassessment can add a layer of safety, but the timing and frequency of reassessment needs to be individualized.[2]World Gastroenterology Organisation. World Gastroenterology Organisation global guidelines: coping with common GI symptoms in the community. May 2013 [internet publication]. http://www.worldgastroenterology.org/guidelines/global-guidelines/common-gi-symptoms/common-gi-symptoms-english

The nomenclature for dyspepsia is confusing. This is largely because some medical organizations include all UGI symptoms in the term dyspepsia, then separate patients with symptoms suggesting GERD for appropriate management, whereas others recognize the overlap in symptoms between the various causes of UGI symptoms but choose to separate the symptoms suggesting GERD before applying the term dyspepsia. Both approaches recommend identifying patients whose symptoms suggest GERD and managing them as having reflux disease.

The American College of Gastroenterology and the Canadian Association of Gastroenterology have published joint guidelines for the management of dyspepsia.[3]Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017 Jul;112(7):988-1013. https://journals.lww.com/ajg/fulltext/2017/07000/ACG_and_CAG_Clinical_Guideline__Management_of.10.aspx http://www.ncbi.nlm.nih.gov/pubmed/28631728?tool=bestpractice.com  The operational definition for dyspepsia used in the guideline is predominant epigastric pain. The authors recognize that patients may present with nausea, vomiting, or fullness but, providing that the patient’s primary concern is epigastric pain, they should be managed as patients with dyspepsia.

A technical review from the American Gastroenterological Association for the evaluation of dyspepsia excludes patients with symptoms that suggest GERD, and includes only those with the typical symptoms.[4]Talley NJ, Vakil NB, Moayyedi P. AGA technical review: evaluation of dyspepsia. Gastroenterology. 2005 Nov;129(5):1756-80. http://www.gastrojournal.org/article/S0016-5085%2805%2901818-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/16285971?tool=bestpractice.com The American College of Gastroenterology have published separate guidance on the diagnosis and management of GERD, which excludes the management of functional heartburn and other functional upper gastrointestinal symptoms.[5]Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. https://journals.lww.com/ajg/fulltext/2022/01000/acg_clinical_guideline_for_the_diagnosis_and.14.aspx http://www.ncbi.nlm.nih.gov/pubmed/34807007?tool=bestpractice.com ​ The UK National Institute for Health and Care Excellence guideline on GERD and dyspepsia in adults suggests a discrete algorithm for patients with symptoms typical of GERD.[6]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Oct 2019 [internet publication]. http://www.nice.org.uk/guidance/cg184

Classification of dyspepsia

Patients with dyspepsia can be classified based on the type or outcomes of the investigations they have received. Research papers often refer to different categories of patients with dyspepsia, so it is important to understand the descriptions of the most common subgroups that have been described.

Uninvestigated dyspepsia is classified as a condition with characteristic symptoms clinically assessed to be originating in the upper gastrointestinal (UGI) tract, but which has not been recently investigated by UGI endoscopy.[3]Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017 Jul;112(7):988-1013. https://journals.lww.com/ajg/fulltext/2017/07000/ACG_and_CAG_Clinical_Guideline__Management_of.10.aspx http://www.ncbi.nlm.nih.gov/pubmed/28631728?tool=bestpractice.com [4]Talley NJ, Vakil NB, Moayyedi P. AGA technical review: evaluation of dyspepsia. Gastroenterology. 2005 Nov;129(5):1756-80. http://www.gastrojournal.org/article/S0016-5085%2805%2901818-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/16285971?tool=bestpractice.com [6]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Oct 2019 [internet publication]. http://www.nice.org.uk/guidance/cg184 ​ Symptoms include epigastric pain or burning, early satiety and postprandial fullness, belching, bloating, nausea, or discomfort in the upper abdomen.

Functional dyspepsia (sometimes called nonulcer dyspepsia) refers to a situation where investigations have not revealed a potential cause for the dyspepsia.[7]Black CJ, Paine PA, Agrawal A, et al. British Society of Gastroenterology guidelines on the management of functional dyspepsia. Gut. 2022 Sep;71(9):1697-723. https://gut.bmj.com/content/71/9/1697.long http://www.ncbi.nlm.nih.gov/pubmed/35798375?tool=bestpractice.com ​ It is generally reserved for patients with a normal endoscopy whose symptoms do not suggest GERD. Patients with GERD with normal endoscopy are said to have nonerosive reflux disease.[3]Moayyedi PM, Lacy BE, Andrews CN, et al. ACG and CAG clinical guideline: management of dyspepsia. Am J Gastroenterol. 2017 Jul;112(7):988-1013. https://journals.lww.com/ajg/fulltext/2017/07000/ACG_and_CAG_Clinical_Guideline__Management_of.10.aspx http://www.ncbi.nlm.nih.gov/pubmed/28631728?tool=bestpractice.com [4]Talley NJ, Vakil NB, Moayyedi P. AGA technical review: evaluation of dyspepsia. Gastroenterology. 2005 Nov;129(5):1756-80. http://www.gastrojournal.org/article/S0016-5085%2805%2901818-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/16285971?tool=bestpractice.com ​​[5]Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. https://journals.lww.com/ajg/fulltext/2022/01000/acg_clinical_guideline_for_the_diagnosis_and.14.aspx http://www.ncbi.nlm.nih.gov/pubmed/34807007?tool=bestpractice.com [8]Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006 Aug;101(8):1900-20. http://www.ncbi.nlm.nih.gov/pubmed/16928254?tool=bestpractice.com ​ The American College of Gastroenterology recommends that a diagnosis of nonerosive reflux disease should only be made if endoscopy is performed with the patient off proton pump inhibitors.[5]Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. https://journals.lww.com/ajg/fulltext/2022/01000/acg_clinical_guideline_for_the_diagnosis_and.14.aspx http://www.ncbi.nlm.nih.gov/pubmed/34807007?tool=bestpractice.com

The Rome IV classification subdivides functional dyspepsia into 3 categories:[9]Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology. 2016 May;150(6):1380-92. http://www.ncbi.nlm.nih.gov/pubmed/27147122?tool=bestpractice.com

• Postprandial distress syndrome (PDS), which is characterized by meal-induced dyspeptic symptoms, such as discomfort, pain, nausea, and fullness

• Epigastric pain syndrome (EPS), which refers to epigastric pain, or epigastric burning, that does not occur exclusively postprandially, can occur during fasting, and can even be improved by meal ingestion

• Overlapping PDS and EPS, which is characterized by meal-induced dyspeptic symptoms and epigastric pain or burning.

GERD and dyspepsia are related and may overlap. There is no gold standard for the diagnosis of GERD. The diagnosis is based on a combination of symptom presentation, endoscopic evaluation of esophageal mucosa, reflux monitoring, and response to therapeutic intervention.[5]Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. https://journals.lww.com/ajg/fulltext/2022/01000/acg_clinical_guideline_for_the_diagnosis_and.14.aspx http://www.ncbi.nlm.nih.gov/pubmed/34807007?tool=bestpractice.com ​ It is known that many patients with GERD will have atypical presentations such as epigastric burning or pain, and therefore their symptoms will cause them to be placed into the group of uninvestigated patients with dyspepsia. Among those undergoing endoscopy for typical GERD symptoms, normal mucosa is the most common finding.[5]Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG clinical guideline for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2022 Jan 1;117(1):27-56. https://journals.lww.com/ajg/fulltext/2022/01000/acg_clinical_guideline_for_the_diagnosis_and.14.aspx http://www.ncbi.nlm.nih.gov/pubmed/34807007?tool=bestpractice.com

The extent or severity of the patient's dyspepsia is measured by the patient's report of the impact of symptoms on quality of life and function. The patient's assessment of the severity of dyspepsia usually relates to the degree to which it affects work, sleep, diet, or leisure.[4]Talley NJ, Vakil NB, Moayyedi P. AGA technical review: evaluation of dyspepsia. Gastroenterology. 2005 Nov;129(5):1756-80. http://www.gastrojournal.org/article/S0016-5085%2805%2901818-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/16285971?tool=bestpractice.com [6]National Institute for Health and Care Excellence. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. Oct 2019 [internet publication]. http://www.nice.org.uk/guidance/cg184

Epidemiology

One meta-analysis reported uninvestigated dyspepsia pooled prevalence of 6.9% (Rome criteria IV) and 17.6% (Rome criteria I), respectively.[10]Barberio B, Mahadeva S, Black CJ, et al. Systematic review with meta-analysis: global prevalence of uninvestigated dyspepsia according to the Rome criteria. Aliment Pharmacol Ther. 2020 Sep;52(5):762-73. https://eprints.whiterose.ac.uk/165990/ http://www.ncbi.nlm.nih.gov/pubmed/32852839?tool=bestpractice.com The prevalence of uninvestigated dyspepsia was 1.5-fold higher in women.[10]Barberio B, Mahadeva S, Black CJ, et al. Systematic review with meta-analysis: global prevalence of uninvestigated dyspepsia according to the Rome criteria. Aliment Pharmacol Ther. 2020 Sep;52(5):762-73. https://eprints.whiterose.ac.uk/165990/ http://www.ncbi.nlm.nih.gov/pubmed/32852839?tool=bestpractice.com Prevalence varied between countries, suggesting that environmental, cultural, ethnic, dietary, or genetic influences play a role.[10]Barberio B, Mahadeva S, Black CJ, et al. Systematic review with meta-analysis: global prevalence of uninvestigated dyspepsia according to the Rome criteria. Aliment Pharmacol Ther. 2020 Sep;52(5):762-73. https://eprints.whiterose.ac.uk/165990/ http://www.ncbi.nlm.nih.gov/pubmed/32852839?tool=bestpractice.com

An internet-based cross-sectional health survey found that Rome IV functional dyspepsia is significantly more prevalent in the US (232 [12%] of 1949 responses) than in Canada (167 [8%] of 1988 responses) and the UK (152 [8%] of 1994 responses; p<0·0001).[11]Aziz I, Palsson OS, Törnblom H, et al. Epidemiology, clinical characteristics, and associations for symptom-based Rome IV functional dyspepsia in adults in the USA, Canada, and the UK: a cross-sectional population-based study. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):252-62. http://www.ncbi.nlm.nih.gov/pubmed/29396034?tool=bestpractice.com The subtype distribution was 61% postprandial distress syndrome, 18% epigastric pain syndrome, and 21% overlapping variant with both syndromes; this pattern was similar across countries.

There is evidence of particular concerns relating to functional dyspepsia in women.[12]Flier SN, Rose S. Is functional dyspepsia of particular concern in women? A review of gender differences in epidemiology, pathophysiologic mechanisms, clinical presentation, and management. Am J Gastroenterol. 2006 Dec;101(12 Suppl):S644-53. http://www.ncbi.nlm.nih.gov/pubmed/17177870?tool=bestpractice.com Dyspepsia has been shown to have a significant negative impact on quality of life. The impact relates to changes in sleep, diet, and interference with work and leisure activities. Women who have experienced emotional or physical abuse appear to be particularly vulnerable to developing functional dyspepsia and irritable bowel syndrome (IBS).

There is much overlap between functional dyspepsia and IBS. Patients who have both disorders have a substantially greater symptom burden and are more likely to consult a physician.[13]Vakil N, Stelwagon M, Shea EP, et al. Symptom burden and consulting behavior in patients with overlapping functional disorders in the US population. United European Gastroenterol J. 2016 Jun;4(3):413-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924424 http://www.ncbi.nlm.nih.gov/pubmed/27403308?tool=bestpractice.com