Functional Dyspepsia_Presentation_AACME.pptx

Dyspepsia means pain or discomfort in the upper part of your stomach.

It is also called “indigestion.”

It’s a symptom, not a disease — but it can make eating unpleasant.

1. Functional Dyspepsia and Beyond

2. Functional Dyspepsia Definition Characterized by persistent or recurrent epigastric pain May include early or uncomfortable postprandial fullness Occurs without any known organic cause

3. Functional Dyspepsia Rome IV Diagnostic Criteria Presence of one or more bothersome symptoms: Postprandial fullness Early satiety Epigastric pain or burning Symptoms should be present for ≥ 3 months. There should be no evidence of organic, systemic, or metabolic disease that could explain the symptoms

4. Functional Dyspepsia Epidemiology Prevalence of Dyspepsia : Dyspepsia is a common symptom with a broad differential diagnosis It has a heterogeneous pathophysiology The global prevalence of un-investigated dyspepsia is up to 20 percent Prevalence varies based on the diagnostic definitions used Healthcare-Seeking Behavior : Dyspepsia can significantly impair quality of life Despite the impact, many individuals do not seek medical attention The percentage of people who seek care ranges from 14% to 66% This variability depends on country and race/ethnicity

5. Functional Dyspepsia Proportion of Functional Cases: Up to 80% of individuals with dyspepsia symptoms have functional (idiopathic, nonulcer) dyspepsia Classification as a Gut-Brain Interaction Disorder: Many experts consider it a disorder of gut-brain interaction It is grouped with other symptom-based gastrointestinal conditions such as: Irritable Bowel Syndrome (IBS) Globus sensation Other similar disorders Diagnostic Challenges: Functional dyspepsia is a benign but difficult-to-diagnose gastrointestinal disorder Presents similarly to other gastrointestinal conditions Diagnosis is based on symptom-based Rome IV Criteria

6. Functional Dyspepsia Characteristic Symptoms: Epigastric pain or burning Early satiety (feeling full early while eating) Postprandial fullness (uncomfortable sensation of fullness after meals) Diagnostic Imaging: No structural abnormalities are typically found on imaging or endoscopy Prevalence: Functional dyspepsia affects over 20% of the population

7. Functional Dyspepsia Functional gastrointestinal disorders (FGIDs) are disorders of brain-gut interaction This group of disorders is largely defined by symptoms without an identifiable structural cause Complex interactions among various factors are thought to be the basis of FGIDs. These factors include: The microbiome of the gut Disturbances of mucosal immunity Visceral hypersensitivity and perceptions of pain Central nervous system dysregulation of gastrointestinal afferent signals and motor function Gastroduodenal motor and sensory dysfunction

8. Functional Dyspepsia - Types Functional dyspepsia (FD) is 1 of 4 categories of functional gastroduodenal syndromes Functional dyspepsia is characterized by ≥ 1 of the following symptoms: Persistent or recurrent epigastric pain and/or burning Uncomfortable postprandial fullness Early satiety Functional dyspepsia may be sub-classified into 2 syndromes, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), which often overlap: EPS is characterized by recurrent pain, discomfort, or burning in the upper abdominal region PDS is characterized by a feeling of fullness that is uncomfortable or interferes with the ingestion of a normal-sized meal 16%-35% of patients with functional dyspepsia have been reported to have symptoms of both syndromes

9. Functional Dyspepsia - Risk Factors Several factors are modestly associated with an increased risk of dyspepsia, including female sex, smoking, Helicobacter pylori infection, use of nonsteroidal anti-inflammatory agents, elevated body mass index, acute gastroenteritis, and specific psychiatric comorbidities. Acute gastroenteritis: The association between acute gastroenteritis and the subsequent development of functional dyspepsia is well established Psychologic conditions: Psychologic conditions that are associated with an increased risk of functional dyspepsia include generalized anxiety disorder, somatization, and major depression

10. Functional Dyspepsia - Pathophysiology The pathophysiology of functional dyspepsia is complicated and incompletely understood; potential mechanisms may differ between subtypes of functional dyspepsia (postprandial distress syndrome versus epigastric pain syndrome) Gastric emptying, accommodation, and vagal function: Functional dyspepsia has been associated with motility disorders, including delayed or accelerated gastric emptying, antral hypomotility, gastric dysrhythmias, impaired gastric accommodation in response to a meal, and abdominal vagal dysfunction Visceral hypersensitivity: Individuals with functional dyspepsia can also have visceral hypersensitivity independent of delayed gastric emptying. Visceral hypersensitivity is characterized by a lowered pain threshold in the presence of normal gastric compliance. Gut-brain axis dysfunction: Gut-brain axis dysfunction may play a role in dyspepsia symptoms. Gut-brain axis communication occurs via the hypothalamic pituitary adrenal (HPA) axis and is modulated by alterations in the gut microbiome, gut epithelial cell barrier, immune function, and stress Altered gut microbiome: Alterations in the upper gastrointestinal tract microbiome may lead to the development of dyspepsia and explain the association between acute gastroenteritis and the subsequent development of dyspepsia Duodenal inflammation and immune activation: Gastric and bile acids may cause low grade inflammation that impairs mucosal integrity and results in abnormal gastrointestinal neuroregulation and symptoms of dyspepsia

11. Functional Dyspepsia - Comorbidities Several gastrointestinal disorders deserve special mention because they can be confused with functional dyspepsia and/or coexist with it. These include gastroesophageal reflux disease (GERD), gastroparesis, and irritable bowel syndrome (IBS): GERD: Functional dyspepsia and GERD frequently coexist, with studies suggesting that 9 to 75 percent of patients with functional dyspepsia also experience GERD symptoms Gastroparesis: Functional dyspepsia and gastroparesis may be related disorders that exist along a spectrum. Abnormal gastric emptying is unstable over time, even in individuals with stable symptoms IBS: More than 60 percent of patients with functional dyspepsia also have symptoms of IBS

12. Functional Dyspepsia & MASLD MASLD is considered a public health problem in many countries Affects both adults and children Characterized by hepatic steatosis (fat accumulation in the liver) detected through: Ultrasound (US) Histological examination of the liver Diagnosed in individuals with: No history of excessive alcohol consumption No other causes of liver disease

13. Functional Dyspepsia & MASLD Progression: MASLD can progress to more severe liver conditions, including: Metabolic dysfunction-associated steatohepatitis (MASH) Cirrhosis Hepatocarcinoma (liver cancer) Comorbidities: MASLD is commonly associated with metabolic comorbidities, including: Obesity Insulin resistance Type 2 diabetes mellitus (DM) Other components of metabolic syndrome

14. Functional Dyspepsia & MASLD Clinical Presentation: MASLD is often a silent disease, asymptomatic until advanced stages Studies show lack of specific symptoms in 45%–100% of patients Diagnosis is often made unintentionally in asymptomatic patients: Detected via elevated serum aminotransferase levels Steatosis on ultrasound detected during: routine testing and investigation of other comorbidities related to MASLD Gastrointestinal (GI) Symptoms and MASLD High proportion of MASLD patients (incidentally detected via ultrasound had initially sought medical attention due to functional GI symptoms Patients with functional dyspepsia undergoing ultrasound shown to have high prevalence of fatty liver There is a lack of published data specifically on the prevalence of GI symptoms in the MASLD population

15. Functional Dyspepsia: Evaluation Rome IV criteria: The Rome IV criteria define functional dyspepsia as the presence of one or more of the following symptoms: Epigastric pain, epigastric burning, postprandial fullness, or early satiation and no evidence of structural disease (including at upper endoscopy) to explain the symptoms. The symptoms should have started at least six months before diagnosis and occurred during the last three months. Individuals with these symptoms and a negative diagnostic evaluation likely have functional dyspepsia. Clinicians can presumptively diagnose functional dyspepsia even in individuals who do not explicitly meet the criteria for symptom frequency and duration. Functional dyspepsia subtypes: Rome IV criteria define two subtypes of functional dyspepsia: Postprandial distress syndrome is characterized by bothersome postprandial fullness and/or early satiation. Epigastric pain syndrome Epigastric pain syndrome is characterized by bothersome epigastric pain or burning that is not exclusively postprandial

16. Functional Dyspepsia: Differential diagnosis The differential diagnosis of functional dyspepsia includes organic causes of dyspepsia and other conditions that cause epigastric or abdominal pain Common organic causes of dyspepsia include peptic ulcer disease; medications, such as nonsteroidal anti-inflammatory drugs; and biliary pain. Gastric malignancy is a rare but life-threatening cause of dyspepsia in North America Other common disorders that can present with dyspepsia include gastroesophageal reflux disease, gastroparesis, irritable bowel syndrome, and cardiac ischemia Clinical assessment, laboratory testing, and upper endoscopy differentiate these conditions from functional dyspepsia

17. Rome IV criteria for functional dyspepsia B1. Functional dyspepsia Diagnostic criteria: 1 or more of the following: Bothersome postprandial fullness Bothersome early satiation Bothersome epigastric pain Bothersome epigastric burning No evidence of structural disease (including at upper endoscopy) that is likely to explain the symptoms

18. Rome IV criteria for functional dyspepsia B1a. Postprandial distress syndrome Diagnostic criteria: Must include 1 or both of the following at least 3 days per week: Bothersome postprandial fullness (ie, severe enough to impact on usual activities) Bothersome early satiation (ie, severe enough to prevent finishing a regular-size meal) No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy) Postprandial epigastric pain or burning, epigastric bloating, excessive belching, and nausea can also be present Heartburn is not a dyspeptic symptom but may often coexist Symptoms that are relieved by evacuation of feces or gas should generally not be considered as part of dyspepsia

19. Rome IV criteria for functional dyspepsia B1b. Epigastric pain syndrome Diagnostic criteria: Must include at least 1 of the following symptoms at least 1 day a week: Bothersome epigastric pain (ie, severe enough to impact on usual activities) and/or Bothersome epigastric burning (ie, severe enough to impact on usual activities) No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine investigations (including at upper endoscopy) Pain may be induced by ingestion of a meal, be relieved by ingestion of a meal, or occur while fasting Postprandial epigastric bloating, belching, and nausea can also be present Persistent vomiting likely suggests another disorder Heartburn is not a dyspeptic symptom but may often coexist The pain does not fulfill biliary pain criteria Symptoms that are relieved by evacuation of faeces or gas generally should not be considered as part of dyspepsia

20. Functional Dyspepsia: Management Initial Approach to Dyspepsia Universal testing for H. pylori in individuals presenting with dyspepsia. Initial treatment decisions are based on the results of H. pylori testing. Testing for H. pylori: Active Infection Testing should detect active H. pylori infection. Recommended test types include: Stool antigen assay Urea breath test Biopsy performed during upper endoscopy Test Selection Criteria Primary factor in selecting a test: Whether the patient undergoes upper endoscopy Patients Undergoing Upper Endoscopy Gastric biopsies are performed Biopsies are used to test for H. pylori Patients Not Undergoing Upper Endoscopy Patients who do not require upper endoscopy Patients who underwent endoscopy but did not have biopsies performed In these cases: Noninvasive testing is used: Urea breath test Stool antigen assay

21. Functional Dyspepsia: Management Patients with H. Pylori: Suggested treatment for H. pylori in individuals with dyspepsia who test positive for H. pylori infection Patients should receive an appropriate antibiotic regimen followed by retesting for H. pylori at least four weeks after completing antibiotics to confirm eradication In patients with functional dyspepsia, a strategy of “test and treat” for H. pylori is modestly more effective than placebo for symptom resolution In a meta-analysis of 14 trials with 3903 participants, eradication therapy for H. pylori cured symptoms of functional dyspepsia more effectively than treatment with placebo or antisecretory therapy plus placebo antibiotics (relative risk [RR] of symptoms not being cured 0.91; 95% CI 0.89-0.94; number needed to treat [NNT] = 14) Compared with placebo or antisecretory therapy plus placebo antibiotics (16 studies; 4424 participants), H. pylori eradication therapy was also more efficacious for symptom improvement (RR of symptoms not improving 0.86; 95% CI 0.79-0.94; NNT = 7).

22. Functional Dyspepsia: Management Patients without H. Pylori: For individuals with a normal initial evaluation for dyspepsia who test negative for H. pylori or who remain symptomatic four weeks after eradication of H. pylori, suggested treatment with a once-daily proton pump inhibitor (PPI) for four to eight weeks Both low- and standard-dose PPIs effectively treat dyspepsia symptoms; high-dose (twice-daily) PPIs do not appear more effective than standard doses In patients whose symptoms improve with the PPI, typically continue treatment for six months and then ask patients to taper and discontinue the PPI Although long-term PPI therapy is generally safe, individuals with functional dyspepsia on chronic PPI therapy should try to discontinue PPIs every 6 to 12 months.

23. Functional Dyspepsia: Management Neuromodulators: In patients with functional dyspepsia whose symptoms do not improve after eight weeks of PPI therapy, initiate a trial of a low-dose neuromodulator, most commonly a tricyclic antidepressant (TCA) or the atypical antidepressant mirtazapine Prefer a TCA because more robust evidence exists to support its efficacy for functional dyspepsia However, mirtazapine is an alternative for patients who are at risk for TCA-related side effects, such as cardiotoxicity (eg, QT interval prolongation) or orthostatic hypotension. Mirtazapine has also demonstrated benefit in the treatment of functional dyspepsia and may be especially useful in those with early satiety, postprandial fullness, or concomitant weight loss For patients with a partial response to a PPI, the TCA can be added to PPI therapy; otherwise, the PPI should be discontinued. TCAs: Begin with a low-dose TCA (eg, amitriptyline 10 mg, nortriptyline 10 mg, or desipramine 25 mg at night) and increase the dose at two- to three-week intervals Many individuals respond to a dose of 20 to 30 mg. Typically do not exceed a dose of 50 mg because higher doses can cause daytime sedation and other anticholinergic side effects and may not be more effective than lower doses The typical duration of a treatment trial is 8 to 12 weeks. If the patient responds, the TCA is continued for six months and then slowly tapered off Patients with recurrent dyspepsia symptoms can resume the same medication

24. Functional Dyspepsia: Management Prokinetic agents: Typically start with metoclopramide 5 to 10 mg three times daily one-half an hour before meals and at night and limit the duration of treatment to four weeks. If symptoms recur, repeat a course of therapy Results of gastric emptying studies should not guide therapy because the relationship between gastric emptying and treatment efficacy has not been established. Up to 30 percent of patients have side effects with prokinetic agents Although most adverse effects are mild and resolve with cessation of therapy, the risk of tardive dyskinesia increases with increasing patient age and the cumulative dose and duration of treatment Prokinetic agents may improve symptoms of functional dyspepsia and are relatively well tolerated In a meta-analysis of 29 trials of participants with functional dyspepsia, symptoms improved more frequently with prokinetics compared with placebo (40 versus 26 percent) However, prokinetics did not improve quality of life, and the quality of evidence was low. All agents except cisapride were well tolerated over the short term. No eligible studies assessed the efficacy of metoclopramide or domperidone, which are the only agents available in North America Methodologic challenges in study design complicate the evaluation of prokinetics for treating functional dyspepsia These include a lack of validated endpoints, variable presence of delayed gastric emptying, and the frequent overlap of functional dyspepsia with GERD

25. Functional Dyspepsia: Management Psychotherapy: For individuals whose symptoms persist despite initial treatment, encourage psychotherapy, especially for patients whose symptoms are exacerbated by psychosocial stressors or who are motivated to try psychotherapeutic interventions Dietary modification: The efficacy of dietary interventions for managing functional dyspepsia is unclear. The postprandial timing of symptoms suggests a role for dietary modification; however, studies have not identified specific foods that trigger functional dyspepsia. Dietitians may help some patients through individualized approaches Antiemetic agents: Patients with predominant postprandial nausea may benefit from a trial of other antiemetic agents, such as promethazine, prochlorperazine, or meclizine; however clinical trial data supporting their efficacy are lacking Fundic relaxant drugs: Limited evidence suggests that relaxing the gastric fundus may improve early satiation and postprandial fullness Antinociceptive agents: Antinociceptive agents, such as pregabalin, carbamazepine, or tramadol, may affect the central processing of pain and thereby decrease visceral hypersensitivity in patients with functional dyspepsia Bioelectric neuromodulation: Bioelectric neuromodulation with auricular vagal nerve stimulation may improve symptoms of functional dyspepsia Virtual reality: In a pilot study of participants meeting Rome IV criteria for functional dyspepsia, three dimensional audiovisual programs administered at least daily for two weeks improved upper gastrointestinal symptoms, compared with sham intervention. Adverse effects were minor. These findings need confirmation in larger trials

26. Functional Dyspepsia: Management Complementary and alternative medicines: Complementary and alternative medicines with possible efficacy for treating functional dyspepsia include peppermint and caraway In a randomized trial of 95 patients with functional dyspepsia, a combination of L-menthol and caraway oil improved symptoms in the subset of participants with epigastric pain syndrome Acupuncture may also have efficacy in alleviating symptoms of functional dyspepsia. A meta-analysis of randomized trials suggested that acupuncture as an adjunct to conventional pharmacotherapy was superior to conventional pharmacotherapy alone in improving symptoms of functional dyspepsia Herbal supplements: A combination of peppermint and caraway oils may offer some benefit for functional dyspepsia Iberogast contains extracts of nine herbs. It may relieve gastrointestinal spasms and improve the intestine’s ability to move food A Japanese herbal remedy called rikkunshito also may be helpful. Researchers found it improved belly pain, heartburn and bloating better than placebo. A placebo is a treatment with no therapeutic effect that looks the same as, and is given the same way as, the medicine or treatment being tested in a study.

27. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Artichokes (Cynara scolymus) have a long history of medicinal use Especially used for liver support and digestive health. Traditional uses are now substantiated through recent research Demonstrated benefits include: Blood sugar metabolism Cholesterol metabolism Liver health

28. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Mechanisms Health benefits may derive from: Phytochemicals in artichokes, such as: Phenolic compounds, Flavonoids Prebiotic fiber: Notably inulin Artichokes promote: Bile secretion and excretion: Aids fat digestion & Aids fat-soluble vitamin digestion Removal of: Toxins, Cholesterol, Xenobiotics and other metabolites Functions: Hepatoprotective Potential: Liver support and protection Promotion of normal body mass index Reduced risk of obesity-related complications Improve liver status in individuals with existing liver damage

29. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Evidence from Systematic Review and Meta-Analysis Review included eight studies on artichoke supplementation Population: Patients with nonalcoholic fatty liver disease (MASLD) and other metabolic conditions Focused on impact on liver enzyme concentrations: Alanine transaminase (ALT) Aspartate aminotransferase (AST) Significance of ALT and AST: Biomarkers for liver function Indicators of MASLD and metabolic syndrome Dosage and duration: Artichoke servings ranged from 100 mg/day (up to 2,700 mg/day) Duration ranged from 4 to 12 weeks

30. Functional Dyspepsia: Management Artichokes (Cynara scolymus): With the exception of one randomized, controlled trial that used metformin as the placebo, the other seven studies showed artichoke leaf extract elicited significant positive effects on liver enzyme levels compared to the placebo Artichoke significantly reduced AST concentrations in those with MASLD and significantly reduced ALT levels in overweight/obese patients or MASLD Another randomized clinical trial published in Phytotherapy Research analyzed the effects of co administration of artichoke leaf extract supplementation (ALES) with metformin and vitamin E in subjects with MASLD Patients were randomly divided into either a metformin-vitamin E group, a metformin-ALES group, or a vitamin E-ALES group After 12 weeks, ALT and AST were significantly reduced within all study groups and the rate of liver fat accumulation was also significantly reduced within all study groups Although larger clinical trials are needed, these results suggest that concomitant administration of artichoke leaf extract, vitamin E, and metformin may help ameliorate MASLD complications Although the exact mechanisms are not fully elucidated, researchers believe the lipid and blood sugar supportive actions of artichokes and their antioxidant and anti-inflammatory properties may explain the ability to favorably affect liver enzyme levels and impart hepatoprotective effects Along with diet and lifestyle changes, supportive herbs, such as artichoke extract, may help promote normal body weight and support liver health, along with improving other risk factors for metabolic and cardiovascular diseases Maintaining a healthy liver also aids in supporting the capacity of the body to detoxify environmental toxins, metabolic waste, heavy metals, and other xenobiotics

31. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Efficacy of artichoke leaf extract in the treatment of patients with functional dyspepsia: a six week placebo-controlled, double-blind, multicentre trial Aliment Pharmacol Ther. 2003 Dec;18(11-12):1099-105. This study aimed to assess the efficacy of artichoke leaf extract (ALE) in the treatment of patients with functional dyspepsia (FD) The ALE preparation tested was significantly better than the placebo in alleviating symptoms and improving the disease-specific quality of life in patients with functional dyspepsia

32. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Phytotherapy with a mixture of dry extracts with hepato-protective effects containing artichoke leaves in the management of functional dyspepsia symptoms Minerva Gastroenterol Dietol. 2010 Jun;56(2):93-9. The aim of the study was to explore the potential of phytotherapy with artichoke leaf extract in the management of functional dyspepsia symptoms, a disorder notoriously recalcitrant to pharmacotherapy Phytotherapy with Cinarepa holds promise as an alternative option in the relief of functional dyspepsia symptoms and merits further investigation in controlled studies

33. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Phytotherapy with a mixture of dry extracts with hepato-protective effects containing artichoke leaves in the management of functional dyspepsia symptoms Minerva Gastroenterol Dietol. 2010 Jun;56(2):93-9. The aim of the study was to explore the potential of phytotherapy with artichoke leaf extract in the management of functional dyspepsia symptoms, a disorder notoriously recalcitrant to pharmacotherapy Phytotherapy with Cinarepa holds promise as an alternative option in the relief of functional dyspepsia symptoms and merits further investigation in controlled studies

34. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J Altern Complement Med. 2004 Aug;10(4):667-9. doi: 10.1089/acm.2004.10.667. Does artichoke leaf extract (ALE) ameliorate symptoms of Irritable bowel syndrome (IBS) in otherwise healthy volunteers suffering concomitant dyspepsia This report supports previous findings that ALE ameliorates symptoms of IBS, plus improves health-related QOL.

35. Functional Dyspepsia: Management Artichokes (Cynara scolymus): Artichoke leaf extract reduces mild dyspepsia in an open study Phytomedicine. 2002 Dec;9(8):694-9 P ost-marketing study indicated that high doses of standardised artichoke leaf extract (ALE) may reduce symptoms of dyspepsia. To substantial these findings, this study investigated the efficacy of a low-dose ALE on amelioration of dyspeptic symptoms and improvement of quality of life Health-related quality of life was significantly improved in both groups compared with baseline. Conclude that ALE shows promise to ameliorate upper gastro-intestinal symptoms and improve quality of life in otherwise healthy subjects suffering from dyspepsia

36. Q & A