Physician Scripps Clinic / Scripps Green Hospital La Jolla, CA
Quan M. Nhu, MD, PhD1, David J. Leung, MD, MS2, Claire P. Witmer, MD3, Nguyen D. Nguyen, MD3, Pooja Magavi, MD1, Faizi Hai, MD1, Loan Duong, BS4, Stephanie X. Dong, BS4, Steve B. Min, MD3, Seema S. Aceves, MD, PhD4, Fouad J. Moawad, MD1; 1Scripps Clinic / Scripps Green Hospital, La Jolla, CA; 2Scripps Mercy Hospital, San Diego, CA; 3Walter Reed National Military Medical Center, Bethesda, MD; 4UC San Diego, La Jolla, CA
Introduction: Eosinophilic esophagitis (EoE) is a chronic antigen-driven, male-predominant (3:1) esophageal disease. We hypothesized that adult EoE females have less fibrostenotic severity and complications, partially due to potential protective effects of estradiol. Methods: A retrospective chart review of EoE clinical course and treatment response patterns focused on sex-stratified clinical, endoscopic and histologic outcomes over ~5 years at 2 academic centers. EoE-derived esophageal fibroblasts were treated with TGFβ1 without or with estradiol and analyzed for profibrotic gene expression by qPCR. Results: In 174 adult EoE patients (129 M, 45 F, M:F 2.9:1), ER visits occurred in 25.3% (M 27.9%, F 20%, p=0.1402), with males making up 83.3% of total EoE ER visits (M:F 5:1). Food impaction occurred in 30.5% of patients (M 33.3%, F 22.2%, p=0.1448), with males making up 82.7% of the total impaction episodes (M:F 4.8:1). Dysphagia (92.3%; M 92.2%, F 92.7%) and chest pain/heartburn (57.1%; M 55.5%, F 62.5%, p=0.3683) were the predominant symptoms. Mean baseline EREFS scores were M 3.2 ± 2.0, F 2.5 ± 1.9 (p=0.0503). Baseline esophageal eosinophils/hpf were similar: M 42.5 ± 30.5, F 43.8 ± 26.9. At 6 months post-treatment, females had lower mean EREFS scores (F 1.6 ± 0.9 vs M 3.0 ± 1.5, p=0.0201) and lower esophageal eosinophil counts (F 10.7 ± 16.3 vs M 36.0 ± 34.2, p=0.0036). Both dysphagia (M 59.3% vs baseline 92.2%, p< 0.0001, F 55.6% vs baseline 92.7%, p=0.0135) and chest pain/heartburn (M 26.9% vs baseline 55.5%, p=0.0168, F 22.2% vs baseline 62.5%, p=0.0323) improved similarly between males and females. Overall combined treatment response was consistently better in females (67-79%) compared to males (35.5-56.4%) between 3 months and >12 months (p = 0.0057). Males were more likely to be nonresponders to treatments: responders M:F 2:1 vs nonresponders M:F 5:1. In EoE-derived esophageal fibroblasts (N=8), estradiol treatment ex vivo inhibited TGFβ1-induced α-sma mRNA expression (p < 0.0001). Discussion: Male EoE patients have a higher burden of disease. EoE females are more likely to respond to treatment with clinical, endoscopic and histologic response. We recently demonstrated a similar pattern in a pediatric EoE cohort, with responders M:F 1:1 vs nonresponders M:F 6:1 (Collins et al, JACI 2019). Our findings have implications in the clinical management of EoE and imply the presence of intrinsic female sex-specific protective mechanisms that warrant further investigation.
Disclosures: Quan Nhu indicated no relevant financial relationships. David Leung indicated no relevant financial relationships. Claire Witmer indicated no relevant financial relationships. Nguyen Nguyen indicated no relevant financial relationships. Pooja Magavi indicated no relevant financial relationships. Faizi Hai indicated no relevant financial relationships. Loan Duong indicated no relevant financial relationships. Stephanie Dong indicated no relevant financial relationships. Steve Min indicated no relevant financial relationships. Seema Aceves indicated no relevant financial relationships. Fouad Moawad indicated no relevant financial relationships.