BACKGROUND & AIMS: The impact of the esophageal eosinophilic distribution pattern on treatment outcomes in eosinophilic esophagitis (EoE) is unclear. We aimed to determine if the eosinophil distribution at index endoscopy predicts proton pump inhibitor (PPI) response in EoE.

METHODS: This was a cohort study of newly diagnosed adult patients with EoE from 3 hospitals. All included patients received ≥8-week PPI trial and underwent repeat biopsies to assess response. Primary analyses compared PPI response between isolated distal disease (≥15 eosinophils/hpf on distal but not proximal biopsies) and proximal/diffuse eosinophilia (≥15 eosinophils/hpf on proximal ± distal biopsies). Secondary analyses categorized patients as distal-predominant (distal >proximal eosinophils by ≥10/hpf), proximal predominant (proximal >distal eosinophils by ≥10/hpf), or even distribution pattern. Multivariable analyses were performed using logistic regression, adjusting for potential confounders.

RESULTS: A total of 266 patients (50.8% male; 89.1% White) met inclusion criteria, including 66 with isolated distal and 200 with proximal/diffuse disease. PPI response was higher among patients with isolated distal disease (histologic remission [<15 eosinophils/hpf post-PPI]: 63.6% vs 44.5%; P = .01; deep remission [<6 eosinophils/hpf]: 54.5% vs 31.0%; P = .001; symptom improvement: 92.4% vs 81.0%; P = .03). On multivariable analyses, isolated distal disease remained independently associated with histologic response (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.10-3.77; P = .02), deep remission (aOR, 2.46; 95% CI, 1.33-4.54; P = .02), and symptom improvement (aOR, 4.1; 95% CI, 1.4-12.01; P = .01). On secondary analyses, proximal-predominant eosinophilia independently predicted PPI histologic nonresponse compared with distal-predominant (aOR, 0.52; 95% CI, 0.28-0.99; P = .04) or any nonproximal (aOR, 0.54; 95% CI, 0.3-0.97; P = .04) pattern.

CONCLUSIONS: Isolated distal eosinophilia at index endoscopy independently predicted PPI response in patients with EoE, whereas proximal-predominant pattern predicted nonresponse. Patterns of esophageal eosinophilic distribution may reflect different disease phenotypes and help guide management.