How to treat eosinophilic esophagitis in a patient allergic to budesonide, proton pump inhibitors (PPIs), and Dupixent (dupilumab)?

Treatment of Eosinophilic Esophagitis with Allergies to Standard Therapies

Given allergies to budesonide, PPIs, and dupilumab, you should pursue elimination diet therapy as your primary treatment approach, specifically starting with a six-food elimination diet under dietitian supervision, with endoscopic dilation reserved for symptomatic strictures. 1, 2

Primary Treatment: Elimination Diet Therapy

Elimination diets are effective in achieving clinico-histological remission in both adults and pediatric patients and represent a viable first-line alternative when medications cannot be used. 2

Specific Dietary Approach

• Initiate a six-food elimination diet (SFED), which removes milk, wheat, egg, soy, nuts, and seafood, as this achieves higher histological remission rates than two or four food elimination diets 2
• Mandatory dietitian involvement: Support from an experienced dietitian throughout both the elimination and reintroduction process is strongly recommended, as the psychological impact of dietary therapy should be appreciated and discussed with patients 2, 3
• Duration: Maintain the elimination diet for 8-12 weeks before performing endoscopic and histological assessment 3
• Reintroduction protocol: After achieving remission, systematically reintroduce foods one at a time under dietitian guidance to identify specific triggers 3

Alternative Dietary Options if SFED Fails

• Consider an elemental diet (amino acid-based formula) if the six-food elimination diet is ineffective, though this has the highest efficacy but lowest compliance and should be reserved for refractory cases 1
• Step-down approach: If SFED achieves remission, you can attempt a less restrictive diet during maintenance 1

Alternative Topical Corticosteroid: Fluticasone

Since the patient is allergic to budesonide specifically, consider fluticasone as an alternative topical corticosteroid. 4

• The AGA/JTF guidelines evaluated both topical budesonide and topical fluticasone, with eight double-blind placebo-controlled studies showing topical glucocorticosteroids (including fluticasone) failed to induce histologic remission in only approximately one-third of treated patients 4
• Fluticasone formulation: Use swallowed fluticasone propionate (typically from asthma inhalers) mixed with a viscous vehicle or administered as a metered-dose inhaler without spacer, swallowed rather than inhaled 4, 5
• Dosing: Administer twice daily for 8-12 weeks before assessing histological response 1
• Safety profile: Short-term studies of ≤3 months showed no increased risk of adverse events compared with placebo, though local viral and fungal infections can occur 4

Management of Fibrostenotic Complications

If the patient develops dysphagia from strictures, endoscopic dilation is effective and safe for improving symptoms. 1, 2

• Endoscopic dilation can be performed using either balloon or bougie dilators with a pooled perforation rate of approximately 0.4% 1
• Critical point: Best outcomes are achieved when endoscopic dilation is combined with effective anti-inflammatory therapy, so continue dietary elimination or fluticasone therapy alongside dilation 1, 2

Monitoring Strategy

Perform repeat endoscopy with biopsy at 8-12 weeks after initiating treatment to assess histological response, as symptoms do not always correlate with histological activity. 2, 3

• Target histologic threshold: Aim for <15 eosinophils per high-power field to define adequate therapeutic response 4
• If symptoms recur during treatment: Repeat endoscopy for assessment and obtain further histology 1, 3

Therapies to Avoid in This Patient

Do not use the following agents, as they are not recommended for EoE management: 2, 5

• Systemic corticosteroids (unfavorable safety profile for chronic use)
• Sodium cromoglycate, montelukast, and antihistamines (ineffective for EoE, though may help concomitant atopic disease)
• Immunomodulators like azathioprine
• Anti-TNF agents (infliximab), vedolizumab, or anti-IL-5 agents (mepolizumab, reslizumab, benralizumab) - these have shown lack of efficacy or unfavorable profiles 2, 5

Refractory Disease Management

If dietary therapy and fluticasone both fail, consider referral to a gastroenterologist and specialist allergist for joint management. 1, 2

• Novel biologics beyond dupilumab (such as cendakimab targeting IL-13 or benralizumab) show promise but are currently investigational and recommended only for patients with coexisting allergic diseases who have failed standard therapies 1, 5
• Anti-IL-13 monoclonal antibody cendakimab has demonstrated significant reduction in eosinophil count and dysphagia scores in phase 2 trials 1

Critical Pitfalls to Avoid

• Do not rely on symptom improvement alone - always confirm histological response with endoscopy, as symptoms may improve without adequate control of inflammation, potentially leading to progressive fibrosis 4, 2
• Do not abandon maintenance therapy - relapse rates are high after withdrawal of successful treatment, and untreated inflammation may progress to fibrostenotic disease 1, 6
• Do not underestimate dietary therapy burden - the psychological impact including anxiety and depression related to persistent symptoms and social restrictions should be discussed upfront 3