Hereditary Angioedema (HAE)
A rare genetic condition causing recurrent severe swelling episodes in skin, GI tract, and airways due to excess bradykinin production. Icatibant, a bradykinin B2 receptor antagonist, is self-administered subcutaneously to treat acute attacks, typically providing relief within 30-60 minutes.
Technical Context
HAE types: Type I (85% — reduced C1-INH levels, <50% normal), Type II (15% — normal C1-INH levels but dysfunctional protein), Type III (rare — normal C1-INH, associated with Factor XII mutations or unknown cause, primarily affects women). Pathophysiology: C1-INH deficiency → uncontrolled contact system activation → excessive bradykinin generation → bradykinin B2R activation → vascular permeability → angioedema. Attack locations: subcutaneous (face, extremities, genitalia — painful, disfiguring), abdominal (intestinal wall oedema — severe pain, mimicking surgical abdomen), and laryngeal (life-threatening airway obstruction — mortality rate approximately 25-40% if untreated). Icatibant mechanism: competitive B2R antagonist → immediate blockade of bradykinin-mediated vascular leakage. Dosing: 30mg SC into abdominal area, onset of symptom relief typically within 30-60 minutes, may repeat after 6 hours if needed. Self-administration training enables patients to treat attacks promptly. Other HAE treatments: C1-INH replacement (plasma-derived or recombinant), lanadelumab (anti-kallikrein antibody for prophylaxis).