Hereditary Angioedema

Hereditary Angioedema results from mutations in genes encoding C1-esterase inhibitor (C1-INH), Factor XII, or other components of contact system regulation, leading to dysregulation of bradykinin production. C1-INH deficiency accounts for approximately 85% of cases (types I and II), with type I involving reduced C1-INH production and type II involving dysfunctional C1-INH protein. Bradykinin mediates vascular permeability changes, leading to angioedema. Swelling episodes are unpredictable and triggered by trauma, stress, menstruation, infections, or occur spontaneously. Skin swelling is typically non-pitting and non-pruritic, distinguishing it from allergic angioedema and urticaria. Abdominal attacks can cause severe pain mimicking acute abdomen and may require unnecessary surgery if not recognized. Most serious is airway swelling, which can be rapidly progressive and life-threatening, potentially requiring intubation. Attacks typically last 24-72 hours, though some persist longer. Patients often have a family history, though de novo mutations occur.