Inflammatory memory as a potential driver of rosacea pathogenesis: integrating mechanisms of chronic relapse and perspectives on disease modification.

Inflammatory memory refers to functional changes retained by a tissue after an inflammatory episode that allow faster or stronger responses to subsequent challenges. It encompasses epigenetic memory in epithelial and stem cells, trained immunity, and tissue-resident memory T cells. Rosacea is a chronic inflammatory skin disease characterized by recurrent flushing, persistent erythema, and papulopustular lesions, and relapse after treatment cessation is common; the mechanisms that drive recurrence remain unclear. In this hypothesis-generating critical review, we use inflammatory memory as an integrative framework and examine evidence consistent with inflammatory memory in rosacea, including the Toll-like receptor 2/kallikrein-related peptidase 5/cathelicidin antimicrobial peptide (LL-37) positive feedback axis, mast-cell-mediated amplification, neuroimmune amplification, and an interleukin-1β-centered persistent inflammatory program. We draw on mechanistic evidence from psoriasis and atopic dermatitis related to tissue-resident memory T cells, epithelial memory, and trained immunity, while explicitly separating established rosacea-specific observations from indirect cross-disease parallels and speculative claims. A multilayer memory network model is proposed in which repeated triggers write memory and lower the relapse threshold; disease modification is then discussed as a candidate therapeutic goal, together with potential strategies and testable hypotheses. Direct molecular evidence for inflammatory memory in rosacea is still lacking, alternative mechanisms remain plausible, and disease modification should be viewed as a perspective rather than an established endpoint.