Public Health and Epidemiology: Open Access
Autonomic Priming as a Potential Disease Modifier in Eosinophilic Oesophagitis A Progressive Three-Hit Hypothesis
Abstract
Bruce H. Knox
Eosinophilic oesophagitis (EoE) is an antigen-driven, Th2-mediated inflammatory disorder characterised by oesophageal dysfunction and mucosal eosinophilia (≥15 eosinophils per high-power field). Although epithelial barrier dysfunction and allergen exposure are established pathogenic drivers, significant heterogeneity exists in symptom severity, motility impairment, and therapeutic responsiveness.
This paper proposes that cumulative autonomic injury may function as a disease-modifying substrate capable of lowering inflammatory activation thresholds in antigen-driven oesophageal disease. Sequential autonomic insults—including viral injury, haemodynamic instability, and cardiothoracic surgical stress—may establish sustained parasympathetic impairment and baroreflex dysfunction. Progressive visceral autonomic involvement may impair oesophageal motility, mucosal clearance, and epithelial integrity, thereby facilitating amplification of antigen-driven Th2 inflammatory responses.
A conceptual three-hit model is proposed in which (1) early autonomic disturbance primes visceral regulatory pathways, (2) haemodynamic stress compounds autonomic instability, and (3) subsequent physiological injury consolidates a persistent dysautonomic state capable of modifying immune activation thresholds.
This framework generates testable predictions linking autonomic dysfunction severity to inflammatory burden and disease variability in eosinophilic oesophagitis.