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

Abstract and Introduction


Purpose of Review: Management for patients with refractory eosinophilic esophagitis (EoE) remains a clinical challenge. This review aims to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the approach to these patients.

Recent Findings: Many patients will fail first-line therapies for EoE. Longer duration of therapy can increase response rates, and initial nonresponders may respond to alternative first-line therapies. There are ongoing clinical trials evaluating novel therapeutics that hold promise for the future of EoE management. Increasingly, there is recognition of the contribution of oesophageal hypervigilance, symptom-specific anxiety, abnormal motility and oesophageal remodelling to ongoing clinical symptoms in patients with EoE.

Summary: For refractory EoE, clinicians should first assess for adherence to treatment, adequate dosing and correct administration. Extending initial trials of therapy or switching to an alternative first-line therapy can increase rates of remission. Patients who are refractory to first-line therapy can consider elemental diets, combination therapy or clinical trials of new therapeutic agents. Patients with histologic remission but ongoing symptoms should be evaluated for fibrostenotic disease with EGD, barium esophagram or the functional luminal imaging probe (FLIP) and should be assessed for the possibility of oesophageal hypervigilance.


Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease defined by symptoms of oesophageal dysfunction and increased eosinophils of at least 15 per high-powered field (hpf) on histopathology in the absence of other diseases that can cause oesophageal eosinophilia.[1] Adults most commonly present with dysphagia, food impactions and chest pain, but children can present with a variety of nonspecific symptoms such as feeding difficulties, failure to thrive and vomiting.[2,3] Unfortunately, there are still no FDA-approved therapies for EoE, and treatment options include dietary approaches, off-label use of medications and oesophageal dilation.[4,5] No currently available treatment approach is completely effective, and the management of patients who are refractory to standard therapy remains a clinical challenge. The goals of this review are to define refractory EoE, explore rates and reasons for nonresponse, and discuss the evidence that informs the current approach to these patients.