VISUAL MECHANISM SUITE for The Calcium–Pericyte–Pseudohypoxia Axis: Reframing Topical Steroid Rebound Phenomena.

Topical steroid rebound phenomena is a pericyte driven vascular normoxic pseudohypoxia.This structured visual suite explains the mechanistic underpinnings of Topical Steroid Rebound Phenomena (TSRP) through a novel systems-level model: the Calcium–Pericyte–Pseudohypoxia Axis. Moving beyond traditional barrier-focused explanations, this model reframes steroid-induced injury as a vascular-metabolic signaling failure, centered on pericyte-mediated vasoconstriction, calcium dysregulation, and pseudohypoxic HIF activation under normoxic conditions. Each panel provides a key layer of mechanistic clarity: Figure 1: Pseudohypoxia: Pericyte-Mediated Collapse in TSRP Demonstrates how glucocorticoid receptor (GR) activity suppresses VIP and NO signaling, maintaining pericyte constriction and promoting HIF-1α stabilization despite normoxia—an upstream origin of rebound. Figure 2: Mechanistic Model of TSRP: Pericyte Dysfunction and Terrain Collapse Breaks down the structural sequence: blanching (efficacy marker) → calcium-locked pericytes (mechanism) → pseudohypoxic terrain failure and multisystem dysregulation (outcome). Figure 3: The Pathophysiology of Collapse: The 1 + 2 = 3 Equation Summarizes the entire rebound cascade using a simple visual heuristic. Blanching + Pericyte Constriction = Pseudohypoxia and Rebound, with downstream consequences including mast cell priming, volatile entrapment, and systemic inflammation. Together, these graphics consolidate a coherent explanatory model for steroid-induced rebound that accounts for vascular signaling, tissue oxygenation, and terrain-wide destabilization. This submission is intended to support translational research, clinical reframing, and educational dissemination around steroid injury.