Clinical and histopathological correlates of elevated ligands of receptors for advanced glycation end products and type 2 cytokines in acquired reactive perforating collagenosis

Acquired reactive perforating collagenosis (ARPC) is driven by synergistic pathways involving metabolic stress and type 2 inflammation. Metabolic disorders (e.g. diabetes, renal failure) elevate advanced glycation end products (AGEs) and HMGB1, which activate the receptor for AGEs (RAGE) signalling. Concurrently, IL-4/IL-13 promote STAT6 phosphorylation, enhancing S100A8/A9 expression. These pathways converge via RAGE, leading to aberrant collagen synthesis and transepidermal elimination.