Background

Hereditary angioedema (HEA) is a rare genetic disorder characterized by attacks of severe swelling. These swellings can effect the arms, legs, face and airway. Swellings of the airway can cause obstruction and can be life-threatening when untreated. Attacks can occur every two weeks and last for a few days without preventive measurements.  

The underlying cause for these symptoms are a deficiency in functional C1-inhibitor. C1-inhibitor inactivates different proteins within the complement system and contact activation system. The activation of the contact activation system leads to the generation of bradykinin. Bradykinin receptors are expressed on endothelial cells and responsible for the active transfer of fluid into localized tissues, which in the end results in edema.  

Current treatment 

Currents treatments are effective, but are still not able to normalize patients’ lives. Antifibrinolytic agents and attenuated androgen are used as short- and long-term prophylactic agents. These drugs can inactivate bradykinin and increase production of functional C1-inhibitor. Treatment options for acute attacks are limited to supportive care and efforts to protect the airway.  

C1-esterase inhibitor 

The first approved targeted prophylactic therapy was plasma-derived C1-inhibitor. This therapy can be administered at infusion centers or at home via self-administration.  

Illustration: https://www.nejm.org/doi/full/10.1056/NEJMra1808012