Monitoring Eosinophilic Esophagitis Disease Activity With Blood Eosinophil Progenitor Levels

Since a minimally invasive biomarker for disease is desperately needed in eosinophilic esophagitis (EoE), the purpose of this study was to evaluate if peripheral circulating eosinophil progenitors (EoP) could be used as a biomarker for active disease in pediatric EoE patients.

Thirty-four total samples from 31 individuals were included in the final analysis. The study participants included pediatric patients, ages 4 to 17 years, including 18 individuals with inactive EoE and 16 with active EoE at the time of endoscopy. Most patients were white boys (70% boys; 97% white), which is consistent with the known disease demographics.

In this prospective observational study, peripheral blood samples, symptom history, and laboratory data were collected from pediatric patients undergoing endoscopy for evaluation of EoE on dietary therapy at Cincinnati Children’s Hospital. Peripheral blood EoP level was determined by flow cytometry. Participants were eligible if they met 2017 consensus EoE diagnostic guidelines (3) (>15 eosinophils per high-power field [eos/HPF] and a failed proton-pump inhibitor [PPI] trial) and were managed with dietary therapy without the use of topical steroids. Active EoE disease was defined as peak eosinophil counts ≥15 eosinophils/HPF in esophageal biopsies, taken the same day as the blood to assess EoP by flow cytometry.

EoP levels (EoPs per 10⁶ gated events) in the peripheral blood were 3-fold higher in patients with active EoE than inactive EoE (P < .0025). Blood absolute eosinophil count did not distinguish between active and inactive EoE (P = .16). A cut-off EoP level 17 accurately detected active disease in 79% of patients with 94.4% specificity and 62.5% sensitivity (area under the curve 0.81; P < .0024). Antihistamine use lowered the threshold EoP level to detect active EoE. If patients were not taking antihistamine, the cut-off level of ≥17 accurately detected active disease 100% of the time. Active allergic rhinitis or atopic dermatitis did not influence circulating EoP levels as much as active EoE.

EoP circulating blood levels may be promising as a biomarker to detect active EoE disease in patients undergoing food trials and potentially reduce the need for repeated endoscopies. Since EoP level is affected by antihistamines, larger prospective studies are needed to investigate the effects of antihistamines and swallowed steroids on EoP mobilization into the peripheral blood.

Although this study shows patients with EoE on dietary therapy have a higher EoP with active disease, the levels in the peripheral blood are overlapping, and, although statistically significant, the sensitivity of the assay is low, indicating active patients could be missed if this biomarker was used alone as a marker for active disease. EoP definitely shows promise but needs further validation. The antihistamine effect is interesting because it is possible that histamine blockage may modulate the Th2 response that mobilizes eosinophils into the periphery. This would need further investigation to prove. Future studies will need to include a control group and determination if EoP is just as indicative of active EoE in patients who are nonresponsive to dietary therapy. This study suggests use of a biomarker of histologic inflammation like EoP might decrease the need for endoscopy and anesthesia exposure in select patients with EoE in the future.