What's the next step for an adult patient with nausea, no vomiting, stable weight, and mild esophagitis shown on Esophagogastroduodenoscopy (EGD), who didn't improve with Proton Pump Inhibitor (PPI) therapy?

Next Step: Refer to Gastroenterology for Upper Endoscopy with Esophageal Biopsies

For an adult patient with persistent nausea, mild esophagitis on EGD, and no improvement with PPI therapy, the next step is referral to gastroenterology for repeat upper endoscopy with multiple esophageal biopsies to exclude eosinophilic esophagitis (EoE), as this presentation is highly suggestive of PPI-refractory disease requiring objective diagnostic evaluation. 1, 2

Why This Patient Needs Referral Now

This patient meets clear criteria for specialist referral after failing 4-8 weeks of PPI therapy 1, 2. The American Gastroenterological Association explicitly recommends against continuing empiric therapy beyond this timeframe without objective testing 1. The combination of:

• Persistent nausea despite PPI treatment
• Mild esophagitis that should have responded to acid suppression
• Stable weight (ruling out malignancy concerns)
• No vomiting (suggesting this is not gastroparesis)

...creates a diagnostic puzzle that requires endoscopic re-evaluation with biopsies 3.

The Critical Diagnostic Consideration: Eosinophilic Esophagitis

The most important diagnosis to exclude is eosinophilic esophagitis, which can present with nausea and mild esophageal inflammation but will not respond to PPI therapy alone. 3 Adults with typical GERD symptoms refractory to PPIs generally do not need repeat endoscopy unless they have clinical features suggesting EoE, such as atopy or food-related symptoms 1. However, this patient's complete lack of response to PPI with persistent nausea warrants biopsy evaluation.

The endoscopist must obtain at least 5 esophageal mucosal biopsy specimens from multiple levels of the esophagus to adequately evaluate for eosinophilic esophagitis 3. A single prior EGD showing only "mild esophagitis" without biopsies is insufficient to rule out EoE, as the endoscopic appearance can be subtle 3.

What the Gastroenterologist Will Do

Upon referral, the diagnostic workup will proceed systematically 1, 2, 4:

Upper Endoscopy with Biopsies

• Assess for erosive esophagitis severity (Los Angeles classification) 3
• Evaluate for Barrett's esophagus 1
• Measure hiatal hernia size 3
• Obtain multiple esophageal biopsies (minimum 5) to exclude eosinophilic esophagitis 3
• Look for alternative diagnoses (peptic ulcer disease, gastric pathology) 3

If Endoscopy Shows Normal Findings or Only Mild Changes

The next step would be prolonged wireless pH monitoring off PPI therapy (96-hour Bravo capsule preferred) to confirm whether true GERD exists or if the patient has a functional esophageal disorder 3, 4. The PPI should be discontinued for 2-4 weeks before testing 4.

Interpretation of pH monitoring results: 4

• Acid Exposure Time (AET) <4.0% on all days = Not GERD, likely functional heartburn or reflux hypersensitivity
• AET >4.0% on ≥1 day = Confirms true GERD
• Los Angeles B or greater esophagitis and/or ≥2 days with AET >6% = Strong GERD diagnosis

Esophageal Manometry

May be performed to exclude achalasia and assess peristaltic function, particularly if the patient develops dysphagia or if invasive interventions are being considered 1, 4.

Common Pitfalls to Avoid

Do not continue empiric PPI dose escalation or switch to different PPIs without establishing a definitive diagnosis. 1, 4 This patient has already failed standard PPI therapy, and further empiric trials are low yield 1.

Do not assume all esophageal inflammation is acid-related. 3 Eosinophilic esophagitis can mimic GERD endoscopically but requires entirely different treatment (topical steroids or dietary elimination) 3. Missing this diagnosis leads to months of ineffective PPI therapy.

Do not add adjunctive medications (H2 blockers, prokinetics, alginates) empirically without objective confirmation of the underlying problem. 3, 4 The AGA explicitly states that adjunctive pharmacotherapy should be personalized to the GERD phenotype, not used empirically 3, 4.

Do not perform pH monitoring while on PPI as the initial diagnostic test - testing should be done off PPI to establish whether GERD truly exists 4.

Why Nausea Without Vomiting Matters

Isolated nausea in the setting of mild esophagitis and PPI failure is atypical for uncomplicated GERD 5. While nausea can occur with GERD, it is not the predominant symptom, and its persistence despite PPI therapy suggests either:

1. The nausea is not acid-related (pointing toward EoE, functional disorder, or gastroparesis)
2. There is inadequate acid suppression (though this is less likely given stable weight and no progression)
3. A non-GERD diagnosis is responsible 3, 5

The stable weight is reassuring and argues against gastroparesis or malignancy 1. The absence of vomiting makes gastroparesis less likely, though it cannot be completely excluded 5.

What Happens If EoE Is Diagnosed

If biopsies reveal ≥15 eosinophils per high-power field, the diagnosis is eosinophilic esophagitis 3. Treatment options include:

• PPI therapy at high doses (which paradoxically can work for EoE through anti-inflammatory mechanisms, not acid suppression) 3
• Topical corticosteroids (budesonide or fluticasone) 3
• Dietary elimination therapy 3

Importantly, 61% of patients with EoE show clinical response to PPI therapy, but this requires confirmation of histologic remission with repeat endoscopy 3. Long-term PPI therapy is appropriate for PPI-responsive EoE 3.

Timeline for Action

Referral should be made promptly - within 1-2 weeks - as this patient has already spent sufficient time on empiric therapy without benefit 1, 2. Multimodality evaluation can change the diagnosis in 34.5% of PPI-refractory cases and guide alternative therapies in 42% of patients 1.