Functional Dyspepsia: How to Manage the Burn and the Bloat (Part I)

Note: This article is reprinted from the Cleveland Clinic Journal of Medicine (2024;91[5]:301-307). It represents the first portion of the published journal article, with a review of the pathophysiology and symptoms of functional dyspepsia and diagnostic tips. Part II will focus on the treatment of functional dyspepsia.

Written by Scott Gabbard, MD and Nina Vijayvargiya, BS

Functional dyspepsia is defined as persistent symptoms of postprandial bloating, early satiety or pain in the center of the upper abdomen, without findings on upper endoscopy such as peptic ulcer disease to explain these symptoms. It is common, affecting up to 30% of the global population, but it often goes undiagnosed for years. There are two subtypes: epigastric pain syndrome (burning and pain) and postprandial distress syndrome (bloating and satiety). The authors discuss how to diagnose and treat both subtypes.

Two categories

Dyspepsia refers to a group of symptoms in the upper region of the gastrointestinal tract. Functional dyspepsia (i.e., not due to an identifiable abnormality) can be divided into two categories:

• Postprandial distress syndrome (fullness or early satiety after meals)
• Epigastric pain syndrome (epigastric burning or pain).¹

While many patients and clinicians assume that dyspeptic symptoms indicate peptic ulcer disease, recent studies have found that up to 85% of patients with dyspeptic symptoms have normal findings on upper endoscopy.²

The global prevalence of functional dyspepsia ranges between 10% and 30%.³ Risk factors include female sex, high socioeconomic status, older age, living in a rural location, using nonsteroidal inflammatory drugs and being married. Smoking is weakly associated with functional dyspepsia, whereas coffee and alcohol consumption have no known association with it.^1,3

Functional dyspepsia vs. irritable bowel syndrome

Irritable bowel syndrome is a disorder of recurring abdominal pain combined with bowel movement changes (constipation, diarrhea or both). It is similar to functional dyspepsia in many ways: symptoms are related to diet, there are often psychiatric comorbidities and treatments are similar. Hence, irritable bowel syndrome is often misdiagnosed as functional dyspepsia. However, functional dyspepsia refers to symptoms in the upper abdomen, whereas irritable bowel symptoms present in the lower abdomen and are connected to changes in bowel habits.⁴

The two conditions can overlap. A 2022 study from Australia found that 45% of patients with functional dyspepsia also met the criteria for irritable bowel syndrome.⁵ A careful discussion with the patient is required to tease out specific symptoms of functional dyspepsia and irritable bowel syndrome so that they are treated optimally.

Pathophysiology

The pathophysiology of functional dyspepsia, like that of all disorders of gut-brain interaction, is poorly understood. However, there are clear associations with visceral hypersensitivity, disruptions of normal gastro duodenal motility, or both. Potential mechanisms include the following:

Delayed gastric emptying can be found in 25% to 35% of patients with functional dyspepsia.^1,6 However, some patients with functional dyspepsia actually have rapid gastric emptying.⁷

Abnormal gastric accommodation. Normally, gastric accommodation is modulated by food consumption triggering the vagovagal response and nitrergic nerve excitement in the gastric wall. This process is often impaired in patients with functional dyspepsia, who may experience uneven gastric food distribution, antral pooling of chyme, and reduced proximal reservoir content. After eating, up to a third of patients with functional dyspepsia have impaired gastric accommodation.^1,8

Hypersensitivity in response to chemical and mechanical stimulation in the upper bowel and stomach is common in cases of functional dyspepsia, and this hypersensitivity is suspected to occur in response to stimuli such as lipids and intraluminal acid.¹

H pylori infection can retrospectively be presumed to be the cause of functional dyspepsia if the symptoms resolve after the organism is eradicated. However, eradicating H pylori does not guarantee that dyspepsia will go away: in various studies, between seven and 15 patients needed to undergo H pylori eradication for one case of functional dyspepsia to be resolved.^9,10

Gut microbiome dysbiosis. Numerous studies have found a strong link between gut microbiome dysbiosis and functional dyspepsia, as the biological barrier and immune functions of the intestinal mucosa are disrupted. The microbiota in the gastrointestinal tract and mouth have been shown to be imbalanced in patients with functional dyspepsia, and small intestinal bacterial overgrowth has been associated with functional dyspepsia. Damage to the intestinal mucosal barrier increases its permeability and thereby decreases its ability to block noxious substances. Additionally, studies have found microinflammatory cell infiltration in the duodenum of more than 40% of patients with functional dyspepsia.^11,12

Environmental factors. Eosinophilia in the duodenum and a correlation with early satiety have been observed in patients with functional dyspepsia. Changes in permeability and inflammation in the duodenal mucosal lining have been associated with stress, food allergies, smoking, infection and acid exposure.¹

Psychological component. A relationship between psychiatric disease, anxiety, depression and functional dyspepsia has been confirmed, and a relationship between functional dyspepsia and neuroticism is often acknowledged.¹ Troubles managing life affairs and experiencing emotional and physical abuse as an adult may contribute to functional dyspepsia. Because having a functional gastrointestinal disease makes a patient more susceptible to psychological issues, the relationship is probably bidirectional.

Criteria for diagnosis

The Rome Foundation is a global initiative that creates guidelines for diagnosing and treating functional gastrointestinal conditions. The Rome criteria were initially developed for research, but more recent iterations have also focused on clinical care. The most recent update, Rome IV,^1,13 was released in 2016. The Rome IV criteria for functional dyspepsia are as follows:

• Patients must present with symptoms of postprandial fullness, epigastric burning, epigastric pain or early satiation; for postprandial distress syndrome, patients must experience postprandial fullness affecting daily activities or early satiation affecting their ability to consume a normal-size meal at least three days each week; for epigastric pain syndrome, patients must experience epigastric pain or burning, or both, affecting daily activities at least one day each week
• There should be no sign of a structural problem (including at upper endoscopy) that could be correlated with symptoms
• Symptoms must be present for at least six months, and diagnostic criteria must be met for three months.^1,13

Regarding testing, current guidelines suggest upper endoscopy for patients age 60 and older to rule out malignancy. However, routine upper endoscopy to rule out malignancy is not recommended for patients under age 60, as their risk of cancer is less than 1% even if they have alarm features.¹⁰ For patients younger than 60, noninvasive testing for H pylori such as stool antigen assay is recommended.^10,14

Symptoms can wax and wane

Although symptoms of functional dyspepsia can be managed, it is a lifelong medical condition that can wax and wane over time. The aim of treatment is to improve quality of life by decreasing or eliminating symptoms. Patients can often reduce the dosage or even stop treatments once their symptoms resolve. It is, however, reasonable to expect symptom exacerbations throughout the life span, especially in response to stress or triggers, which may require patients to restart treatment.¹⁵ Importantly, functional dyspepsia has not been shown to affect long-term survival.¹⁶

References

1. Stanghellini V, Chan FK, Hasler WL, et al. Gastroduodenal disorders. Gastroenterology 2016; 150(6):1380–1392.
2. Nasseri-Moghaddam S, Mousavian AH, Kasaeian A, et al. What is the prevalence of clinically significant endoscopic findings in subjects with dyspepsia? Updated systematic review and meta-analysis. Clin Gastroenterol Hepatol 2023; 21(7):1739–1749.e2
3. Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroenterol 2006; 12(17):2661–2666.
4. Cremonini F, Talley NJ. Review article: the overlap between functional dyspepsia and irritable bowel syndrome—a tale of one or two disorders? Aliment Pharmacol Ther 2004; 20(suppl 7):40–49.
5. Jones MP, Shah A, Walker MM, Koloski NA, Holtmann G, Talley NJ. Overlap of heartburn, functional dyspepsia, and irritable bowel syndrome in a population sample: prevalence, temporal stability, and associated comorbidities. Neurogastroenterol Motil 2022; 34(9):e14349.
6. Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut 2014; 63:1972–1978.
7. Gomez Cifuentes J, Radetic M, Lopez R, Gabbard S. Clinical predictors of rapid gastric emptying in patients presenting with dyspeptic symptoms. Dig Dis Sci 2019; 64(10):2899–2909.
8. Tack J, Piessevaux H, Coulie B, et al. Role of impaired gastric accommodation to a meal in functional dyspepsia. Gastroenterology 1998; 115:1346–1352.
9. Kang SJ, Park B, Shin CM. Helicobacter pylori eradication therapy for functional dyspepsia: a meta-analysis by region and H. pylori prevalence. J Clin Med 2019; 8(9):1324.
10. Moayyedi P, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N. ACG and CAG clinical guideline: management of dyspepsia [published correction appears in Am J Gastroenterol 2017; 112(9):1484]. Am J Gastroenterol 2017; 112(7):988–1013.
11. Zhou L, Zeng Y, Zhang H, Ma Y. The role of gastrointestinal microbiota in functional dyspepsia: a review. Front Physiol 2022; 13:910568.
12. Nojkov B, Zhou SY, Dolan RD, et al. Evidence of duodenal epithelial barrier impairment and increased pyroptosis in patients with functional dyspepsia on confocal laser endomicroscopy and “ex vivo” mucosa analysis. Am J Gastroenterol 2020; 115(11):1891–1901.
13. Rome Foundation. The Rome IV criteria. Appendix A: Rome IV diagnostic criteria for FGIDs. https://theromefoundation.org/rome-iv/rome-iv-criteria/. Accessed April 17, 2024.
14. Dore MP, Pes GM. What is new in Helicobacter pylori diagnosis: an overview. J Clin Med 2021; 10(10):2091.
15. Sayuk GS, Gyawali CP. Functional dyspepsia: diagnostic and therapeutic approaches. Drugs 2020; 80(13):1319–1336.
16. Ford AC, Forman D, Bailey AG, Axon AT, Moayyedi P. Effect of dyspepsia on survival: a longitudinal 10-year follow-up study. Am J Gastroenterol 2012; 107(6):912–921.