Topical steroid rebound phenomena (TSRP) is a pericyte driven vascular normoxic pseudohypoxia, with backwards bifurcation and hysteresis.ABSTRACT: This paper presents the core mechanisms for the scope of impact explored in Decoding TSRP: The Pericyte Connection (doi.org/10.5281/zenodo.16907869) as the governing causal sequence. This synthesis consolidates those dynamics into a structured three-part equation mapping the interrelation between steroid potency, vascular enforcement, and terrain collapse:1. Blanching = Efficacy2. Calcium-mediated pericyte constriction = Mechanism3. Pseudohypoxia from regulatory failure = Rebound
The Kennedy model establishes rebound as terrain collapse triggered by pericyte-mediated vasoconstriction and its metabolic consequences. This provides a coherent mechanistic account of TSRP and formalizes the 1 + 2 = 3 equation as both explanatory and predictive. These dynamics mirror pseudohypoxic signaling described in fibrotic and neoplastic contexts, where HIF activation proceeds despite normoxia via metabolic or oxidative stress disruption [Bae 2024; Brereton 2022; Hayashi 2018].
Framed as a three-part equation—(1) blanching as pharmacodynamic endpoint, (2) calcium-activated pericyte constriction as mechanism of action, and (3) pseudohypoxic terrain collapse as outcome—the model clarifies the distinction between drug withdrawal and vasoregulatory failure. This concise summary is intended to support conceptual clarity and translational coherence across adjacent fields.Visual Mechanism Suite included.