Updates in hereditary angioedema and chronic spontaneous urticaria.

Abstract

Hereditary angioedema (HAE) is a genetic disorder caused by either deficiency of C1 esterase inhibitor (85% of cases) or normal to high levels of nonfunctional C1 esterase inhibitor. Both defects lead to dysregulation of the kallikrein pathway, unregulated bradykinin production, and episodic swelling involving the skin, abdomen, and, in up to 50% of patients, the airway sometime during their life-span. A newer phenotype, HAE with normal C1 inhibitor (HAE type III), has also been recognized, although its mechanisms remain incompletely defined and diagnosis is largely based on consensus algorithms. Chronic spontaneous urticaria (CSU) is a mast cell-mediated inflammatory skin disorder characterized by transient pruritic wheals; angioedema occurs in up to 40% of patients and may be the only manifestation in 10-20%. HAE and CSU are mechanistically distinct, and misdiagnosis may lead to inappropriate treatment and worse outcomes. This review summarizes recent advances in the pathophysiology of HAE and CSU and how these insights have driven the development of targeted therapies. Emerging precision medicine approaches and greater emphasis on shared decision-making are reshaping management and hold promise for improving clinical outcomes and quality of life in HAE and CSU.