Localized skin edema: etiologies and mechanisms of development

Background. Localized skin edema is a common presentation in the practices of allergists, dermatologists, and family physicians. From an etiopathogenetic perspective, it represents a heterogeneous group of conditions in which an identical phenotype may arise from fundamentally different mechanisms. Identifying the operative mechanism in each patient is crucial for appropriate evaluation and targeted management. Purpose – to synthesize contemporary evidence (2020–2025) on the etiologies and pathogenesis of localized skin edema available in Ukrainian‑ and English‑language sources. Materials and Methods. Narrative literature review using PubMed/MEDLINE, Scopus, Web of Science, Google Scholar, and Ukrainian specialty journals (01.2020–09.2025; languages: Ukrainian and English). Inclusion criteria: reviews, original studies, EAACI/WAO guidelines, consensus statements, and case reports addressing causes/mechanisms of angioedema (localized skin edema). Results. The development of localized skin edema converges on two mechanistic models: histaminergic (mast cell–mediated) and bradykinin‑mediated. The former features mast‑cell activation (immunologic–IgE‑dependent and IgE‑independent–and non‑immunologic), degranulation with release of preformed and secondary mediators. The latter is driven by dysregulation of the kallikrein–kinin system and the complement system due to genetic defects (SERPING1, F12, PLG, and others) and acquired conditions (autoimmune and lymphoproliferative disorders, medication effects). In both models, the principal event is increased microvascular permeability within the (revised) Starling framework, with a decisive role of the endothelial glycocalyx and lymphatic drainage in edema resolution. Conclusions. Distinguishing mast cell–driven and bradykinin‑mediated mechanisms at the levels of triggers and molecular events is key for phenotypic interpretation, enabling clinicians to tailor therapy and follow‑up, and laying the groundwork for subsequent work on diagnostics and targeted treatment. Uniquely, the review considers not only the causes of localized skin edema but also the mechanisms underlying its resolution.