Beyond Swelling: Clinical Insights into the Diagnosis and Management of Hereditary Angioedema

Abstract

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe, non-pitting edema, most commonly caused by a deficiency or dysfunction of C1 esterase inhibitor (C1-INH), resulting in excessive bradykinin production. HAE subtypes differ according to C1-INH levels, functional activity, underlying genetic variants, and increasingly recognized molecular mechanisms. Awareness of HAE outside specialized medical fields remains limited, and recurrent angioedema may arise through different pathophysiological mechanisms, which together contribute to frequent misdiagnosis, particularly in patients without a positive family history. Consequently, many patients experience significant diagnostic delays and inappropriate interventions. Rapid advances in endotype-based classification, molecular diagnostics, and targeted therapies have substantially changed the understanding and management of HAE, highlighting the need for an updated clinical overview. This review provides a comprehensive overview of HAE classification, clinical presentation, genetic background, diagnosis, and current management. Particular attention is given to advances in diagnostic biomarkers and genetic testing, newly approved targeted therapies, and oral on-demand treatment. Together, these advances are moving HAE management toward earlier diagnosis, more individualized treatment, and more patient-centered care.