Functional Dyspepsia

Article Author:
Pilin Francis
Article Editor:
Stacey Zavala
Updated:
4/30/2020 9:01:34 PM
PubMed Link:
Functional Dyspepsia

Introduction

Functional dyspepsia is one of the most common functional gastrointestinal disorders and affects more than 20% of the population.  There are three different subtypes: epigastric pain syndrome (EPS), postprandial distress syndrome (PDS), and overlapping PDS and EPS. Functional dyspepsia is diagnosed based on the Rome IV criteria.  It is defined by the presence of one or more of the following symptoms: epigastric pain or burning, early satiety, and postprandial fullness in the absence of structural disease using imaging or endoscopy.[1][2][3] First, patients should be tested and treated for Helicobacter pylori (H. pylori) if they are less than 60 years of age.[4][5] Then, further treatment consists of symptom management with proton pump inhibitors (PPI), H2 receptor antagonists (H2RA), prokinetic agents, and even antidepressants.[1][4] Alarms symptoms such as weight loss, dysphagia, or vomiting, or if greater than age 60, warrant an endoscopic evaluation.[6]

Etiology

The etiology of functional dyspepsia is likely multifactorial; however, the exact cause is not clearly understood.  Several risk factors have been seen to be associated with the condition.[1]

  • Enteric infections: H. pylori, Escherichia coli O157, Campylobacter jejuni, and Salmonella.
  • Recent antibiotic use
  • Use of non-steroidal anti-inflammatory drugs
  • Being overweight
  • Smoking
  • Psychosocial dysfunction

Epidemiology

Functional dyspepsia prevalence varies worldwide, with higher prevalence in Western countries (10 to 40%), including the United States (US). In Asian countries, the prevalence is 5% to 30%.  Functional dyspepsia is found to be more common in women than in men. This difference is said to be due to inherent sex-specific differences in gastrointestinal function, for example, there exists sex-specific variation in hormone mechanisms, pain signaling, and health care maintenance.[1] 

Pathophysiology

Although the exact mechanism is not well understood, the pathophysiology of functional dyspepsia is complex. Several different mechanisms are thought to contribute to each subtype.[7] Traditionally, functional dyspepsia has been attributed to disturbances in gastric physiologic factors divided into macroscopic and microscopic mechanisms. Macroscopic mechanisms include gastroesophageal reflux (GERD), delayed gastric emptying, and visceral hypersensitivity alterations in the nervous system. Microscopic mechanisms include impaired barrier function, altered sensitivity to duodenal acid or lipids, and gastroduodenal inflammation.[8] Additional mechanisms include environmental insults like food inducing gastroduodenal physiologic changes, infections causing inflammation, and allergen exposure can lead to eosinophil recruitment in genetically predisposed patients. Psychological factors like anxiety and depression can cause a negative stimulus to the brain-gut axis, suggesting that there is central processing of visceral stimuli from sensations in the gastrointestinal tract.[1][3][9][10] 

History and Physical

Typical symptoms can be divided into the subtypes PDS and EPS, and there exists an overlap between the two syndromes. These symptoms can be acute or chronic. PDS patients report loss of appetite, early satiation, nausea, retching, vomiting, and bloating. In EPS, patients have stomach cramping and other upper abdominal pain. Some symptoms are non-gastrointestinal. Patients often report associated diaphoresis, headache, sleep disorders, and irritable bladder.  Functional dyspepsia symptoms usually do not progress and lack red flag signs of unintentional weight loss, dysphagia, night sweats, and persistent vomiting.[3] Patients usually have an unremarkable physical exam, and this can assist in excluding other diagnoses.[11]

Evaluation

To exclude organic causes, evaluation can start with laboratory tests, including blood count, complete metabolic panel, thyroid function, and inflammatory markers. If H. pylori infection is prevalent in at least 10% of the population, it is recommended to test for this.[1] Instrumental examinations include esophagogastroduodenoscopy with biopsy and abdominal ultrasonography. The American College of Gastroenterology (ACG) recommends the routine use of upper endoscopy in patients older than 60 years to rule out malignancy, especially in the setting of red flag signs. If patients do not respond to treatment, it is reasonable to pursue more specialized testing specific to the symptoms.[3]

Confirmation of the diagnosis is based on the patient’s history with the exclusion of other diseases with similar presentations.[3] Rome IV symptom criteria for functional dyspepsia are defined as the presence of one or more of the following symptoms: bothersome postprandial fullness, early satiety, epigastric pain, or burning with no demonstration of structural or metabolic disease to explain the symptoms. Symptoms duration is at least 3 months, with the onset of symptoms occurring at least 6 months before diagnosis. Furthermore, the symptoms can be divided into PDS & EPS based on the primary symptom. PDS is usually meal-induced and presents with postprandial fullness and early satiation, while EPS is characterized by epigastric pain or burning.[1][2][3] 

Treatment / Management

Treatment can be challenging, where the main aim is symptom control.[5][12] Initial management begins with an explanation of the diagnosis and discussing the patient’s expectations for treatment. If it is suspected, H. pylori eradication is recommended as the first treatment for all patients with functional dyspepsia, as this improves symptoms and decreases the risk of peptic ulcers and gastric cancer.[4][5] After this, treatment is a two-step process. The first-line treatment is with a proton pump inhibitor or H2 receptor antagonist for at least four weeks. Then, if symptoms persist, subsequent treatment with tricyclic antidepressants, or prokinetic agents like metoclopramide and acotiamide (not available in the U.S.) are pursued.[5][13][14][15][16][17] Adjunctive or alternative non-pharmacologic therapies include psychotherapy, herbal supplementation, lifestyle modification, dietary interventions, acupuncture, and electrical stimulation.[18]

Differential Diagnosis

  • GERD
  • H. pylori infection
  • Gastritis
  • Peptic ulcer disease
  • Celiac disease
  • Irritable bowel syndrome
  • Small intestinal bacterial overgrowth
  • Chronic pancreatitis
  • Gastroparesis
  • Acute cholecystitis
  • Gastric carcinoma

Prognosis

Functional dyspepsia is relapsing and remitting. Population studies have shown that during extended follow-up, 15% to 20% of patients have persistent symptoms, while 50% have complete resolution of symptoms.  There is no data to show that it is associated with decreased survival.[3][18]

Complications

Although the condition is not associated with increased mortality, it does cause physical and mental distress affecting the patient’s quality of life.[7] It has been found that patients with functional dyspepsia score higher on psychometric tests for symptoms of anxiety, depression, and somatization. About 10% to 25% of patients report the social impact of their symptoms, enough to seek a physician, leading to more health care visits, greater health impairment, and, thus, an overall worse quality of life.[3][19]

Deterrence and Patient Education

It is essential to educate patients on the benign course of this disorder, to establish long-term care and expectations for treatment.[3] If red flag signs such as unintentional weight loss, persistent vomiting, or dysphagia are present, further evaluation is recommended. 

Enhancing Healthcare Team Outcomes

Functional dyspepsia is a rather common condition that prompts a patient to visit their physician. Patients will have symptoms that manifest similarly to other conditions. It is important to rule out any potential organic causes of the symptoms using additional [invasive] testing, especially if red flag signs are present. Making the diagnosis can be difficult, as it is a clinical diagnosis based on the Rome IV criteria.[3] Treatment can be equally as challenging because frequently, symptoms are refractory to first-line treatments. An interdisciplinary team that includes primary care, gastroenterologists, nurses, psychiatrists, and pharmacists can aid in the recognition of this condition. It is important to educate patients on the definition and course of functional dyspepsia, as patient understanding is paramount to treatment. [Level 5] 


References

[1] Enck P,Azpiroz F,Boeckxstaens G,Elsenbruch S,Feinle-Bisset C,Holtmann G,Lackner JM,Ronkainen J,Schemann M,Stengel A,Tack J,Zipfel S,Talley NJ, Functional dyspepsia. Nature reviews. Disease primers. 2017 Nov 3;     [PubMed PMID: 29099093]
[2] Park JK,Huh KC,Shin CM,Lee H,Yoon YH,Song KH,Min BH,Choi KD, [Current issues in functional dyspepsia]. The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi. 2014 Sep 25;     [PubMed PMID: 25252861]
[3] Madisch A,Andresen V,Enck P,Labenz J,Frieling T,Schemann M, The Diagnosis and Treatment of Functional Dyspepsia. Deutsches Arzteblatt international. 2018 Mar 30;     [PubMed PMID: 29669681]
[4] Tomita T,Oshima T,Miwa H, New Approaches to Diagnosis and Treatment of Functional Dyspepsia. Current gastroenterology reports. 2018 Oct 18;     [PubMed PMID: 30338390]
[5] Addula M,Wilson VED,Reddymasu S,Agrawal DK, Immunopathological and molecular basis of functional dyspepsia and current therapeutic approaches. Expert review of clinical immunology. 2018 Oct;     [PubMed PMID: 30235962]
[6] Moayyedi P,Lacy BE,Andrews CN,Enns RA,Howden CW,Vakil N, ACG and CAG Clinical Guideline: Management of Dyspepsia. The American journal of gastroenterology. 2017 Jul     [PubMed PMID: 28631728]
[7] Hantoro IF,Syam AF, Measurement of Health-Related Quality of Life in Patients with Functional Dyspepsia. Acta medica Indonesiana. 2018 Jan;     [PubMed PMID: 29686182]
[8] Ye Y,Wang XR,Zheng Y,Yang JW,Yang NN,Shi GX,Liu CZ, Choosing an Animal Model for the Study of Functional Dyspepsia. Canadian journal of gastroenterology     [PubMed PMID: 29623262]
[9] Talley NJ,Ford AC, Functional Dyspepsia. The New England journal of medicine. 2015 Nov 5;     [PubMed PMID: 26535514]
[10] Talley NJ,Walker MM,Holtmann G, Functional dyspepsia. Current opinion in gastroenterology. 2016 Nov;     [PubMed PMID: 27540688]
[11] Zagari RM,Fuccio L,Bazzoli F, Investigating dyspepsia. BMJ (Clinical research ed.). 2008 Sep 15;     [PubMed PMID: 18794180]
[12] Vakil NB,Howden CW,Moayyedi P,Tack J, White Paper AGA: Functional Dyspepsia. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2017 Aug;     [PubMed PMID: 28529164]
[13] Miwa H,Kusano M,Arisawa T,Oshima T,Kato M,Joh T,Suzuki H,Tominaga K,Nakada K,Nagahara A,Futagami S,Manabe N,Inui A,Haruma K,Higuchi K,Yakabi K,Hongo M,Uemura N,Kinoshita Y,Sugano K,Shimosegawa T, Evidence-based clinical practice guidelines for functional dyspepsia. Journal of gastroenterology. 2015 Feb;     [PubMed PMID: 25586651]
[14] Koduru P,Irani M,Quigley EMM, Definition, Pathogenesis, and Management of That Cursed Dyspepsia. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Apr;     [PubMed PMID: 28899670]
[15] Simrén M,Tack J, Functional dyspepsia: evaluation and treatment. Gastroenterology clinics of North America. 2003 Jun;     [PubMed PMID: 12858607]
[16] Tack J,Masaoka T,Janssen P, Functional dyspepsia. Current opinion in gastroenterology. 2011 Oct;     [PubMed PMID: 21934617]
[17] Vanheel H,Tack J, Therapeutic options for functional dyspepsia. Digestive diseases (Basel, Switzerland). 2014;     [PubMed PMID: 24732188]
[18] Wang YP,Herndon CC,Lu CL, Non-pharmacological Approach in the Management of Functional Dyspepsia. Journal of neurogastroenterology and motility. 2020 Jan 30;     [PubMed PMID: 31751504]
[19] Sahan HE,Yildirim EA,Soylu A,Tabakci AS,Cakmak S,Erkoc SN, Comparison of functional dyspepsia with organic dyspepsia in terms of attachment patterns. Comprehensive psychiatry. 2018 May;     [PubMed PMID: 29501961]