Description

Diagnosis and Management of Esophagogastric Functional Disorders

1.0 Introduction to Esophagogastric Disorders of Gut-Brain Interaction (DGBI)

Patients presenting with upper gastrointestinal symptoms such as heartburn, chest pain, and dyspepsia represent a common and complex clinical challenge. This protocol provides a structured, evidence-based pathway for the clinician to differentiate between structural diseases like gastroesophageal reflux disease (GERD) and a group of conditions defined by the Rome IV criteria as Disorders of Gut-Brain Interaction (DGBI). A core principle of this protocol is that a functional diagnosis is a positive diagnosis, established through a systematic workup that identifies characteristic symptom patterns after excluding organic pathology. It is not, and should not be considered, a mere diagnosis of exclusion when other tests are negative.

The primary esophagogastric DGBI addressed within this protocol include:

Functional Esophageal Disorders:

• Functional Heartburn: Retrosternal burning in the setting of physiologically normal acid exposure and a negative symptom-reflux correlation.
• Reflux Hypersensitivity: Symptoms of heartburn or chest pain triggered by physiologic levels of reflux, confirmed by a positive symptom correlation despite a normal acid exposure time.
• Functional Chest Pain: Retrosternal chest pain of presumed esophageal origin after a cardiac cause has been excluded and in the absence of GERD or a major esophageal motility disorder.
• Globus: A persistent, non-painful sensation of a lump or foreign body in the throat, occurring between meals, without any structural or motor cause.
• Functional Dysphagia: A sensation of abnormal bolus transit through the esophagus in the absence of any mucosal, structural, or major motor disorder.

Functional Gastroduodenal Disorders:

• Functional Dyspepsia: This condition is further divided into two primary subtypes:
  • Epigastric Pain Syndrome (EPS): Characterized by bothersome epigastric pain or burning. 
  • Postprandial Distress Syndrome (PDS): Characterized by bothersome postprandial fullness, early satiety, and/or meal-related bloating.

Initial Triage: The Role of Alarm Features

The first step in evaluating any patient with these symptoms is to screen for alarm features that mandate an expedited workup to rule out serious underlying pathology.

Alarm Features Requiring Immediate Investigation:

• Dysphagia (difficulty swallowing)
• Odynophagia (painful swallowing)
• Gastrointestinal bleeding (hematemesis, melena, or iron-deficiency anemia)
• Unintentional weight loss (>10% body weight in 6 months)
• Age ≥60 years with new-onset dyspepsia
• Family history of upper GI malignancy
• Previous gastric surgery
• Palpable abdominal mass
• Lymphadenopathy
• Persistent vomiting

For patients without alarm features, proceed to the appropriate diagnostic pathway, beginning with the GERD-spectrum evaluation for those presenting with heartburn or chest pain.

2.0 The GERD-Spectrum Diagnostic Pathway

This pathway is strategically designed to systematically determine whether a patient's reflux-like symptoms are caused by pathologic acid reflux (GERD) or by a functional esophageal disorder. This distinction is critical, as it dictates entirely different management strategies. For a patient without alarm features, the initial approach is an empiric trial of acid-suppressive therapy.

The standard initial strategy is an 8-week empiric trial of a once-daily proton-pump inhibitor (PPI). If symptoms persist, the first step is to optimize therapy by escalating to twice-daily (BID) dosing, ensuring the medication is taken 30-60 minutes before meals. If symptoms remain refractory despite this optimization, further diagnostic evaluation is required.

Upper endoscopy is a pivotal diagnostic tool in this pathway. The findings directly determine the next steps in management and diagnosis.

Upper Endoscopy Findings and Management:

• LA Grade C/D Esophagitis, Barrett's Esophagus, or Stricture: These findings confirm GERD diagnosis. Proceed with PPI maintenance therapy. Consider surgical evaluation if refractory to medical management.
• LA Grade A/B Esophagitis: These findings are not conclusive for GERD diagnosis. If symptoms persist despite optimal PPI therapy, proceed to ambulatory reflux monitoring OFF PPI.
• Normal Endoscopy: No evidence of erosive disease. If symptoms persist despite optimal PPI therapy, proceed to ambulatory reflux monitoring OFF PPI to evaluate for non-erosive reflux disease (NERD) vs. functional disorders.

Ambulatory reflux monitoring (via a catheter-based or wireless capsule system) is the definitive test to characterize the relationship between a patient's symptoms and reflux events. The timing of the test relative to PPI therapy is critical and depends on the clinical question.

• Testing OFF PPI (Diagnostic): The purpose of this test is to definitively prove or disprove the presence of pathologic acid reflux. It is performed when a diagnosis of GERD has not yet been established (e.g., in patients with a normal EGD or LA Grade A/B esophagitis).
• Testing ON PPI (Phenotyping): The purpose of this test is to evaluate the cause of persistent symptoms in a patient with proven GERD. It helps distinguish refractory acid reflux from a functional overlap condition.

The results from an OFF-PPI ambulatory reflux study will place the patient into one of three distinct diagnostic categories, each with a unique therapeutic path.

• Abnormal Acid Exposure Time (AET >6%): This result confirms the diagnosis of GERD. If the EGD was normal, the specific diagnosis is non-erosive reflux disease (NERD).
• Normal AET with a Positive Symptom Correlation: This result confirms the diagnosis of Reflux Hypersensitivity. The patient is hypersensitive to physiologic, non-pathologic levels of reflux.
• Normal AET with a Negative Symptom Correlation: This result confirms the diagnosis of Functional Heartburn. The patient's symptoms are not related to reflux events.

Once a diagnosis of proven GERD is established, the management focus shifts to effective and durable symptom control, which presents its own set of challenges in refractory cases.

3.0 Management of Proven and Refractory GERD

For patients with a confirmed diagnosis of GERD (established by LA Grade C/D esophagitis or an abnormal AET), the goal of management is symptom control and healing of the esophageal mucosa. While most patients respond well to standard PPI therapy, a subset will experience persistent symptoms. Management of this cohort demands a systematic approach to optimizing therapy before considering a functional overlap or labeling the condition as truly refractory.

The term "Refractory GERD" is an objective diagnosis, not merely a label for persistent symptoms. The formal definition depends on the patient's baseline findings:

• For patients...