Status quo and future developments in the diagnosis and treatment of hereditary angioedema.

Abstract

Hereditary angioedema (HAE) is a rare hereditary disease characterized by edema, which can be life-threatening in case of swelling in the larynx. The most common form of HAE is caused by a mutation of the SERPING1 gene and is characterized by a deficiency (type I) or loss of function (type II) of the C1 inhibitor (C1-INH), leading to excessive production of bradykinin. In contrast, the HAE-nC1-INH entity is associated with a normal C1-INH protein and is caused by mutations in other genes. Because HAE is a rare and often underdiagnosed disease, it may take years from symptom onset to diagnosis. The angioedema attacks cause suffering and affect both the ability to work and quality of life (QoL). The treatment of HAE includes attack treatment (on-demand), short-term prophylaxis (e.g., before medical procedures), and long-term prophylaxis. Four first-line treatment options for long-term prophylaxis are available, effectively preventing attacks and supporting the guideline goal of complete disease control. Further treatment options, including CRISPR/Cas9-based gene therapy, are under development and promise to provide individually tailored treatment for patients. This review aims to provide an overview of the clinical presentation, diagnosis, and treatment of HAE.