Abstract
A BSTRACT Hereditary angioedema (HAE) is a bradykinin-driven disorder marked by unpredictable, potentially life-threatening edema and evolving therapeutic complexity. Here, we provide an updated, evidence-integrated synthesis of contemporary HAE diagnosis and management (2010 present), combining guideline recommendations, randomized trials, and regulatory data into a unified clinical framework. Diagnosis is reframed as an algorithmic process that integrates clinical phenotyping with complement testing, while highlighting the expanding genetic landscape and diagnostic uncertainty of HAE with normal C1 inhibitor (HAE-nC1INH). Therapeutic paradigms have shifted toward mechanism-based precision interventions, including plasma kallikrein inhibition, factor XIIa blockade, and RNA-targeted therapies, alongside emerging oral on-demand options that enable early, patient-directed treatment. The novelty of this review lies in its integration of rapidly evolving therapeutic classes with practical, guideline-aligned diagnostic and treatment algorithms, while explicitly addressing real-world implementation challenges, including access, monitoring, and patient-centered decision-making. Despite major advances, key gaps remain in biomarker validation, comparative effectiveness, and global accessibility. This work positions HAE as a model for precision medicine in rare diseases and provides a clinically actionable roadmap for translating innovation into practice.