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Clinical Practice Guideline: Diagnosis and Management of Dyspepsia and Peptic Ulcer Disease1.0 Introduction and ScopeDyspepsia represents one of the most common and complex symptom presentations encountered in both primary care and gastroenterology. Its management requires a nuanced understanding of a broad differential diagnosis, ranging from benign functional disorders to life-threatening malignancies. This clinical practice guideline is designed to provide healthcare professionals with a clear, evidence-based, and systematic framework for the evaluation and management of patients presenting with dyspeptic symptoms.The term "dyspepsia" is derived from its Greek etymology: dys- (meaning 'bad' or 'difficult') and pepsis (meaning 'digestion'). It is a symptom complex, not a final diagnosis, characterized by chronic or recurrent discomfort centered in the epigastrium. The core symptoms include bothersome postprandial fullness, early satiation, epigastric pain, and epigastric burning.The primary objectives of this guideline are threefold: to standardize the diagnostic approach to uninvestigated dyspepsia, to provide clear criteria for differentiating between functional and organic etiologies, and to outline rational, stepwise treatment algorithms for both functional dyspepsia and confirmed peptic ulcer disease. By adhering to this structured pathway, clinicians can enhance diagnostic accuracy, optimize resource utilization, and improve patient outcomes.Therefore, a formal classification system is the essential foundation for subsequent diagnostic and therapeutic decisions.2.0 Defining and Classifying DyspepsiaThe strategic importance of classifying dyspepsia cannot be overstated. A proper initial classification into either functional or organic etiologies serves as the cornerstone of effective and efficient patient management, directing the clinician toward appropriate testing, targeted therapies, and realistic prognostic counseling.2.2 Functional Dyspepsia (FD)Functional Dyspepsia (FD) is diagnosed in patients who meet specific symptom criteria in the absence of an identifiable structural cause. It is the most common cause of chronic dyspepsia, accounting for approximately two-thirds of cases.The formal Rome IV diagnostic criteria for Functional Dyspepsia require the presence of one or more of the following symptoms for the last three months, with symptom onset at least six months prior to diagnosis:Bothersome postprandial fullnessEarly satiationEpigastric painEpigastric burningCrucially, a definitive diagnosis of FD requires that there be no evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms, typically confirmed by a normal upper endoscopy.FD is further categorized into two primary subtypes based on the predominant symptom pattern:Postprandial Distress Syndrome (PDS): Characterized by meal-induced symptoms, specifically bothersome postprandial fullness and/or early satiation.Epigastric Pain Syndrome (EPS): Characterized by epigastric pain or burning that is not exclusively related to meals and may occur during fasting.2.3 Organic DyspepsiaOrganic dyspepsia is defined as dyspeptic symptoms that are caused by an identifiable structural, metabolic, or pathological condition. The diagnostic investigation is focused on identifying and treating this underlying cause.Common causes of organic dyspepsia include:Peptic Ulcer Disease (PUD), including both gastric and duodenal ulcersGastric or esophageal cancerErosive gastritis or duodenitisGastroesophageal Reflux Disease (GERD)Pancreatobiliary diseases (e.g., chronic pancreatitis, cholelithiasis)Medication-Induced DyspepsiaA significant subset of organic dyspepsia is directly attributable to medications that injure the upper gastrointestinal mucosa or alter its function. Common offending agents include:Nonsteroidal anti-inflammatory drugs (NSAIDs)AspirinBisphosphonatesIron supplementsMoving from this classification framework, the next step involves the practical diagnostic evaluation of the patient.3.0 Diagnostic Evaluation of Dyspepsia: A Stepwise ApproachA systematic, stepwise diagnostic approach is critical to avoid unnecessary procedures while ensuring the timely identification of serious pathology. The following clinical pathway is recommended for the evaluation of a patient presenting with dyspepsia.3.2 Initial Assessment and Identification of Alarm FeaturesThe first step in the clinical encounter is to confirm the symptom profile and screen for features suggestive of serious underlying disease. It is essential to differentiate true dyspepsia from other conditions. Specifically, clinicians must note that isolated heartburn and regurgitation are the cardinal symptoms of GERD, not dyspepsia.The following "Alarm Features" are critical indicators that mandate prompt and direct endoscopic evaluation:Age ≥60 with new-onset symptomsUnintentional weight lossProgressive dysphagia or odynophagiaAnemia or signs of gastrointestinal bleeding (e.g., melena)Persistent vomitingA palpable abdominal mass or lymphadenopathyA family history of upper gastrointestinal cancer3.3 Diagnostic Pathway for Patients with Alarm Features (or Age ≥60)The first and most appropriate diagnostic step is an Esophagogastroduodenoscopy (EGD) with biopsies for any patient with one or more alarm features, or for any patient aged 60 or older presenting with new-onset dyspepsia, even in the absence of other alarm features. Empiric therapy in this population is inappropriate and may delay the diagnosis of a malignancy.3.4 Diagnostic Pathway for Patients without Alarm Features (and Age <60)In younger patients without alarm features, a more conservative initial approach is recommended to balance efficacy with cost and procedural risk. The preferred strategy involves noninvasive testing and empiric therapy in a sequential manner:H. pylori Testing: The initial step should be noninvasive testing for Helicobacter pylori using either a urea breath test or a stool antigen assay. If the test is positive, the patient should receive a course of eradication therapy.Empiric PPI Trial: If H. pylori testing is negative, or if symptoms persist following successful eradication, the next step is a 4- to 8-week trial of a once-daily Proton Pump Inhibitor (PPI).Referral for EGD: An EGD is warranted only if symptoms remain refractory to both H. pylori eradication (if applicable) and an empiric PPI trial.In a patient with persistent symptoms meeting Rome IV criteria, a normal EGD confirms the diagnosis of Functional Dyspepsia, reinforcing the clinical axiom: Dyspepsia + Normal Endoscopy = Functional Dyspepsia.This structured diagnostic process allows for the confident identification of Functional Dyspepsia, a condition that requires a distinct management approach.4.0 Management of Functional Dyspepsia (FD)Managing Functional Dyspepsia is often challenging and requires a multimodal, stepwise approach that prioritizes patient education and reassurance. The goal is symptom control and improved quality of life, as there is no curative therapy. A strong therapeuti...