Topical steroid rebound phenomena is a pericyte driven vascular normoxic pseudohypoxia.ABSTRACT: This paper is a translational synthesis that consolidates peer-reviewed evidence on pericyte biology from vascular, immune, metabolic, and neuroendocrine research. It organizes these findings into a continuous account showing how pericytes function as systemic regulators whose disruption destabilizes terrain across multiple organ systems. The analysis demonstrates how topical glucocorticoids uniquely corrupt barrier-first pericyte biology through their expression of GR, their dependence on VIP signaling, and their role in cutaneous respiration and volatile clearance. These interactions explain why Topical Steroid Rebound Phenomena (TSRP), historically misnomered TSW, emerges as a systemic recovery state. The paper establishes TSRP as a systemic condition with pericytes as the pivotal cell type mediating collapse and recovery, and provides a coherent biological logic that accounts for rebound phenomena as predictable mechanistic outcomes rather than unexplained pathology.If the work could be distilled and disseminated in a way that reflected the equation of 1+2=3, it is:1. mechanism of efficacy and measure of potency is blanching2. mechanism of action to achieve blanching is vascular constriction through calcium activating pericytes3. mechanism of rebound is hypoxia from prolonged vasoconstriction due to loss of regulationSee also: • Reframing Topical Steroid Rebound: The Calcium-Pericyte-Hypoxia Axis (https://doi.org/10.5281/zenodo.18157705)• The Bioenergetic Cost of Pericytes: The Hidden Axis of Modern Thiamine Deficiency (https://doi.org/10.5281/zenodo.16930406)
Corinna Kennedy (Fri,) studied this question.