What is the role of endoscopic monitoring in patients with eosinophilic esophagitis (EoE) on proton pump inhibitors (PPIs)?

Role of Endoscopic Monitoring in Patients with Eosinophilic Esophagitis on PPIs

Endoscopic monitoring is essential for patients with eosinophilic esophagitis (EoE) on proton pump inhibitors (PPIs) as PPIs can mask underlying disease activity, leading to potential progression of fibrosis and stricture formation despite symptom improvement.

Diagnostic Challenges with PPIs in EoE

PPIs significantly impact the diagnostic accuracy of EoE and can obscure ongoing disease activity:

• PPIs suppress esophageal eosinophilia below the diagnostic threshold of 15 eosinophils per high-power field (hpf) in approximately 51% of patients 1
• This suppression can prevent a definitive diagnosis of EoE when patients undergo endoscopy while on PPI therapy 1
• There is often a disconnect between symptoms and underlying disease activity in EoE patients on PPIs 1

Recommendations for Initial Diagnosis

For accurate diagnosis of EoE:

• PPIs should be withdrawn for at least 3 weeks prior to diagnostic endoscopy and biopsy 1
• This recommendation carries a strong level of recommendation despite very low-grade evidence 1
• Documentation of PPI discontinuation status and duration should be clearly noted on endoscopy reports and histology request forms 1

Monitoring Protocol for EoE Patients on PPI Therapy

When to Perform Follow-up Endoscopy

1. After initial PPI treatment: Even in patients who become asymptomatic on PPI therapy, follow-up endoscopy is warranted to document resolution of eosinophilia 1

2. For patients with persistent symptoms: Endoscopy should be performed to assess disease activity and potential need for additional therapies 1

3. For patients with prior non-diagnostic biopsies but suggestive symptoms/endoscopic findings: Repeat endoscopy should be considered, especially if the patient was on PPI during initial evaluation 1

Rationale for Endoscopic Monitoring Despite Symptom Response

Several factors justify endoscopic monitoring even when patients report symptom improvement on PPIs:

• The chronic nature of EoE where esophageal eosinophilia can lead to progressive fibrosis despite symptom control 1
• Potential discordance between symptoms and underlying biologic disease activity 1
• PPIs may help treat secondary reflux symptoms but might not effectively treat underlying EoE 1

Long-term Outcomes and Monitoring Considerations

Efficacy of PPI Therapy

• Long-term histologic and clinical response rates for PPI therapy are approximately 60% and 64%, respectively 2
• Younger age and prior dilation are associated with loss of histologic response to PPI therapy 2
• Inflammatory EoE phenotype responds better to PPI therapy than stricturing phenotype 3

Disease Progression Concerns

• Delayed diagnosis and treatment of EoE may lead to increased esophageal fibrosis and stricture formation 1
• Patients with a diagnostic delay of more than 20 years have a stricture rate of 71% compared to 17% in those diagnosed within 2 years 1
• Even in patients who don't achieve complete histologic response (<15 eos/hpf) to PPIs, some may still show improvements in lamina propria fibrosis and other histologic parameters 4

Practical Monitoring Algorithm

1. Initial diagnosis: Confirm EoE diagnosis with endoscopy after PPI withdrawal for at least 3 weeks

2. After starting PPI therapy:

   • Perform follow-up endoscopy at 8-12 weeks (extending to 12 weeks may improve response rates) 3
   • Assess both symptom response and histologic response

3. For PPI responders:

   • Consider step-down therapy to determine minimum effective PPI dose 5
   • Continue periodic endoscopic monitoring even with symptom control
   • Most patients can maintain remission with daily PPI doses equal to or below 40 mg of omeprazole 5

4. For PPI non-responders:

   • Consider alternative therapies such as topical corticosteroids 1
   • Maintenance therapy with topical steroids reduces risk of recurrent food bolus obstruction 1

Pitfalls and Caveats

• Symptom-histology disconnect: Symptoms alone are unreliable indicators of disease activity in EoE; 50% of patients with relapsing inflammation may remain in clinical remission 5

• PPI masking effect: A diagnosis of EoE cannot be definitively ruled out in patients who have normal biopsies while on PPI therapy 1

• Phenotype considerations: Patients with stricturing phenotype are less likely to respond to PPI therapy both initially and long-term compared to those with inflammatory phenotype 3

• Monitoring burden: The benefits of endoscopic monitoring must be balanced against potential risks of sedation (especially in children), procedure-related risks, and financial/time burdens 1