Refractory Eosinophilic Esophagitis: What to do When the Patient has not Responded to Proton Pump Inhibitors, Steroids and Diet

Alexandra L. Strauss; Gary W. Falk


Curr Opin Gastroenterol. 2022;38(4):395-401. 

In This Article

What are the Reasons for Nonresponse?

The underlying pathophysiology of EoE is complex, and there is no single therapeutic approach that addresses all aspects of immune dysfunction and subsequent cytokine signalling.[19] In patients failing to respond, it is important to first readdress the accuracy of the diagnosis and assess for secondary causes of oesophageal eosinophilia (Table 2).[1] If the diagnosis remains correct, the next step is to distinguish between patients in histologic remission with ongoing clinical symptoms and patients with both histologic and clinical nonresponse.

For patients with ongoing evidence of histologic inflammation, one should first assess for adherence, dosing and appropriate administration of therapy. Insurance coverage and subsequent cost can be a barrier to compliance, as no pharmacologic treatment option for EoE is FDA-approved. Patients can have difficulty with administration of topical corticosteroids using off-label instructions that are not standardized. Timing of medications can be challenging, especially with topical corticosteroids, that should have adequate time to dwell prior to eating or drinking.[20] Adherence with long-term medications is a challenge. For example, over a 5-year period in one observational study, patients were still taking prescribed maintenance swallowed corticosteroid at only 40% of the visits.[21] Adherence to dietary elimination is similarly difficult with one study showing only a 57% compliance rate. Patients cited difficulty with social situations, diet-related anxiety and perceived diet effectiveness for symptomatic relief.[22] Studies have demonstrated seasonal variation in the diagnosis of EoE, with cases more frequently diagnosed during summer months, suggesting that aeroallergens may contribute to flares.[23–25]

Patients may also have symptoms of oesophageal dysfunction in the setting of complete histologic remission. Remodelling features such as rings and strictures may contribute to clinical nonresponse. A barium esophagram may be a helpful adjuvant study to evaluate for subtle strictures or narrowed oesophagus, which can be missed at the time of endoscopy.[26] Oesophageal dysmotility may cause ongoing symptoms, which can be evaluated with either manometry or the functional luminal-imaging probe (FLIP). In one study of 199 patients with EoE, the contractile response pattern was characterized by FLIP, and only 34% of EoE patients had a normal contractile response with the remaining patients having abnormal contractile response patterns. An abnormal contractile response was associated with fibrostenotic disease, but there was no difference in levels of eosinophils on histology among the different response patterns.[27] Oesophageal hypervigilance and symptom-specific anxiety may contribute to ongoing symptoms in EoE patients. Recent work from the Northwestern group found that hypervigilance and symptom-specific anxiety were the only predictors of increased dysphagia symptoms even when accounting for both histologic and endoscopic variables.[16] Finally, it is important to recognize that patients treated with swallowed steroid preparations may develop odynophagia in the setting of Candida esophagitis, which may be amenable to treatment with antifungal agents.