What is the differential diagnosis for an adult patient with no significant medical history presenting with symptoms of reflux?

Differential Diagnosis of Reflux Symptoms

When an adult with no significant medical history presents with reflux symptoms, the differential diagnosis must distinguish between true gastroesophageal reflux disease (GERD), extraesophageal reflux manifestations, and non-reflux conditions that mimic GERD symptoms.

Primary Diagnostic Categories

True GERD with Esophageal Manifestations

• Erosive esophagitis with visible mucosal breaks on endoscopy 1
• Non-erosive reflux disease (NERD) with normal endoscopy but pathological acid exposure 1
• Barrett's esophagus with columnar metaplasia, though prevalence is only 0.41% in patients aged 30-49 years 1
• Peptic stricture from chronic acid exposure 2

Extraesophageal Reflux (EER) Manifestations

The 2023 AGA guidelines emphasize that 50-60% of patients with suspected EER symptoms will not actually have GERD 1. Common EER presentations include:

• Chronic cough related to micro-aspiration or vagally-mediated airway reactions 1
• Laryngeal symptoms: hoarseness, dysphonia, throat clearing 1
• Asthma exacerbations via reflux or reflex pathways 1
• Dental erosions from acid exposure 1
• Sinus disease and post-nasal drip 1

Critical pitfall: Laryngoscopy findings like arytenoid erythema or edema lack specificity, as these can be present in asymptomatic volunteers and have inconsistent correlation with objective reflux testing 1.

Non-GERD Causes Mimicking Reflux

Esophageal Motility Disorders

• Achalasia should be excluded, particularly if dysphagia is prominent 1, 2
• Ineffective esophageal motility causing symptom perception 1

Eosinophilic Esophagitis

• Must be considered especially when dysphagia accompanies reflux symptoms 1, 2
• Requires endoscopy with biopsy for diagnosis 2

Functional Disorders

• Functional heartburn: normal reflux burden with no symptom-reflux correlation on pH-impedance testing 1, 2
• Reflux hypersensitivity: normal acid exposure but clear symptom correlation with reflux events 1

Gastroparesis and Delayed Gastric Emptying

• Common cause of reflux-like symptoms 1, 2
• May require gastric emptying studies for diagnosis 2

Other Gastrointestinal Conditions

• Peptic ulcer disease requiring endoscopic exclusion 2
• Rumination syndrome with regurgitation of undigested food 1
• Aerophagia causing belching and discomfort 1
• Overlap syndrome with irritable bowel syndrome 1

Diagnostic Approach Algorithm

Step 1: Characterize Symptoms

• Typical GERD symptoms (heartburn described as "burning feeling rising from stomach or lower chest up towards neck" and regurgitation) have 92% sensitivity but only 19% specificity for GERD 3
• Relief with antacids predicts response to PPI therapy 3
• Alarm symptoms (dysphagia, weight loss, bleeding) mandate immediate endoscopy 1

Step 2: Initial Testing Strategy

For patients WITH typical reflux symptoms:

• Trial of single-dose PPI, titrating to twice daily if needed 1
• Upper endoscopy if symptoms persist after 8-12 weeks or if alarm features present 4

For patients WITHOUT typical reflux symptoms but with suspected EER:

• Consider diagnostic testing BEFORE empiric PPI trial 1
• This approach is cost-effective since 50-60% will not have GERD 1

Step 3: Objective Testing When Indicated

Upper endoscopy to:

• Identify erosive esophagitis (Los Angeles grades B, C, D are highly specific for GERD) 1
• Exclude eosinophilic esophagitis, peptic ulcer disease, achalasia 2
• Detect Barrett's esophagus or malignancy 1

Ambulatory reflux monitoring (pH or pH-impedance):

• Off PPI: for diagnosis when GERD is uncertain 1
• On PPI: to evaluate ongoing acid or non-acid reflux in refractory symptoms 1
• pH-impedance preferred over pH-only for EER symptoms, as weak-acidic and non-acidic reflux can cause extraesophageal symptoms 1

Esophageal manometry:

• Primarily to exclude achalasia and assess motility before considering antireflux surgery 1

Key Clinical Pitfalls to Avoid

1. Do not rely solely on symptom improvement with PPI as confirmation of GERD, as this may result from placebo effects or mechanisms other than acid suppression 1

2. Do not assume laryngoscopy findings confirm EER, as erythema and edema lack specificity and inter-rater reliability 1

3. Do not continue empiric PPI trials indefinitely in EER patients—after one 12-week trial without response, proceed to objective testing rather than trying different PPIs 1

4. Do not overlook non-GERD causes in patients with normal endoscopy and negative reflux testing—consider functional disorders, eosinophilic esophagitis, and motility disorders 1, 2

5. In young patients (<50 years) with uncomplicated reflux symptoms, endoscopy is not needed to exclude Barrett's esophagus given its low prevalence (0.41%) in this age group 1

6. No single diagnostic tool conclusively identifies GER as the cause of EER symptoms—diagnosis requires global clinical impression incorporating symptoms, endoscopy, reflux testing, and treatment response 1