What is the next management step for a patient with eosinophilic esophagitis (EoE) not responding to Proton Pump Inhibitors (PPIs) and oral corticosteroids?

Management of Eosinophilic Esophagitis Refractory to PPI and Oral Steroids

For patients with eosinophilic esophagitis (EoE) not responding to proton pump inhibitors (PPIs) and oral corticosteroids, dietary elimination therapy should be the next management step, starting with a two-food elimination diet and progressing to more restrictive diets if needed.

Understanding Treatment-Refractory EoE

When a patient with EoE fails to respond to both PPIs and oral corticosteroids, this represents a challenging clinical scenario that requires a structured approach to prevent progression to fibrostenotic disease.

Rationale for Dietary Management

• Diagnostic delay in EoE is associated with increased risk of fibrostenotic complications, with studies showing progression from 19% in those with diagnostic delay <2 years to 52% with longer delays 1
• Dietary therapy has been shown to induce both symptomatic and histological remission in patients who fail to respond to pharmacological treatments 1

Step-by-Step Management Algorithm

1. Dietary Elimination Approach

• Start with a Two-Food Elimination Diet (TFED):

  • Eliminate milk and wheat or egg for 8-12 weeks
  • This approach achieves histological remission in approximately 43% of patients 1
  • Follow with repeat endoscopy and biopsy to assess response

• If No Response to TFED, Progress to Four-Food Elimination Diet (FFED):

  • Eliminate milk, wheat, egg, and soya for 8-12 weeks
  • This approach achieves remission in approximately 60% of patients 1
  • Perform repeat endoscopy and biopsy

• If No Response to FFED, Progress to Six-Food Elimination Diet (SFED):

  • Eliminate milk, wheat, egg, soya, fish/shellfish, and tree nuts/peanuts for 8-12 weeks
  • This approach achieves remission in approximately 79% of patients 1
  • Perform repeat endoscopy and biopsy

2. Food Reintroduction Process

• Once histological remission is achieved, reintroduce one food at a time for 8-12 weeks
• Perform endoscopy after each reintroduction to identify specific trigger foods 1
• Maintain long-term elimination of identified trigger foods

3. Endoscopic Dilation

• Consider endoscopic dilation for patients with:
  • Reduced esophageal caliber
  • Persistent dysphagia despite histological remission 2
  • Evidence of strictures or fibrostenotic disease

4. Biologic Therapies

• If dietary approaches fail, consider referral for clinical trials of biologic agents targeting specific immune pathways 3, 4
• Dupilumab has shown efficacy in treatment-refractory EoE but should be reserved for cases that fail dietary management 5

Important Considerations

Dietitian Support

• Support from an experienced dietitian is strongly recommended throughout the elimination and reintroduction process 1
• This helps ensure nutritional adequacy and improves adherence to the dietary protocol

Monitoring and Follow-up

• Regular clinical follow-up with symptomatic, endoscopic, and histologic assessment is essential 1
• Even asymptomatic patients require follow-up due to concerns of progression from inflammation to fibrosis 1

Common Pitfalls to Avoid

1. Inadequate trial duration: Ensure each dietary elimination phase lasts 8-12 weeks before assessing efficacy
2. Relying solely on symptoms: Symptom improvement may not reflect histological improvement, so endoscopic assessment is crucial 1
3. Poor patient adherence: The restrictiveness of elimination diets may lead to non-adherence; approximately 28% of patients are unwilling to progress from TFED to FFED, and 39% are unwilling to progress from FFED to SFED 1
4. Overlooking coexisting GERD: EoE and GERD can coexist, and some patients may need treatment for both conditions 1

By following this structured approach to managing refractory EoE, clinicians can optimize outcomes and reduce the risk of disease progression to fibrostenotic complications that significantly impact quality of life.