Hereditary angioedema is a rare,
genetic disorder characterized by painful, debilitating and potentially life-threatening
angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by
prodromal symptoms.
Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of
hereditary angioedema in almost all patients is a mutation in the
SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and
kallikrein-
kinin pathway are insufficiently inhibited, resulting in excessive
bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and
complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders.
Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where
hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific
therapies have greatly improved disease control and
angioedema-related quality of life. This article reviews the clinical picture of
hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options.