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

How do we Define Refractory Eosinophilic Esophagitis?

Despite all of the above best practice guidelines, there is still no standardized definition for either what constitutes response to therapy or refractory EoE. Histologic remission has traditionally been defined as eosinophils less than 15/hpf, but this has not been standardized among clinical trials with varying histologic endpoints. Trials requiring regulatory approval by the FDA have utilized co-primary endpoints of histologic remission (eos <6/hpf) and patient-reported outcomes.[11,12] In addition, Greuter et al.[13] have introduced the concept of deep remission, defined as clinical remission (lack of any EoE attributable symptom under unrestricted dietary habits), histological inflammatory remission (eos <5/hpf) and endoscopic inflammatory remission (complete absence of endoscopic inflammatory features). Furthermore, it is well known that improvement in symptoms does not necessarily correlate with endoscopic or histologic measures of disease activity, especially in patients with fibrostenotic disease.[14,15] Finally, oesophageal hypervigilance and symptom-specific anxiety may contribute to patient-reported symptoms.[16]

To date, there has been no standard definition for refractory EoE. In a previous review by Dellon[17] in 2017, their definition was persistent eosinophilia (≥15 eos/hpf), incomplete resolution of primary presenting symptoms and incomplete resolution of endoscopic findings after treatment. A pragmatic definition by Hirano in 2015 included persistent symptoms, persistent inflammation or both after therapy.[18] Recognizing that definitions for response to therapy are not standardized, we will similarly define refractory EoE as persistent symptoms, persistent oesophageal inflammation on histology or endoscopy, or a combination of both after treatment for EoE.