SUBCUTANEOUS C1-INHIBITOR FOR LONG-TERM PROPHYLAXIS IN HEREDITARY ANGIOEDEMA WITH NORMAL C1 INHIBITOR

Introduction Hereditary angioedema (HAE) is a rare disorder characterized by episodes of swelling without urticaria. HAE presents with decreased C1 inhibitor (C1INH) antigen (type I) or function (type II), or with normal C1INH (HAE-nC1INH). Case Description A 25-year-old female presented with intermittent airway, abdominal and extremity angioedema without hives every 2-4 weeks for 3 years, often coinciding with ovulation or menstruation. She had up to 24 emergency room (ER) visits and 5 hospitalizations annually, historically requiring intubation, abdominal laparoscopy and appendectomy. Pathology revealed normal appendix. C4, ANA, tryptase, C1INH antigen level, C1INH function, C1q and Factor XII gene testing were normal. Angioedema was unresponsive to high-dose antihistamines, systemic corticosteroids, and omalizumab. She was diagnosed with suspected HAE-nC1INH. Progesterone contraceptives and fresh frozen plasma were ineffective. On-demand ecallantide or icatibant reduced episode duration but she continued with frequent symptoms. Prophylactic tranexamic acid and subsequently IV C1INH 1000 units every 3-4 days resulted in modest preventative effects but she had ER visits, hospitalizations and decreased quality of life due to angioedema. In September 2017, she transitioned to prophylactic subcutaneous C1INH replacement 60 IU/kg twice weekly and has since experienced only 3 ER visits with rapid recovery, no hospitalizations, international travel and permanent employment. Discussion Plasma-derived human C1-INH has been reported as a successful acute treatment in HAE-nC1INH. A lower threshold for contact system activation might explain the benefit of higher C1INH levels in some HAE-nC1INH patients. Our report demonstrates that SQ C1INH may be effective for long-term prophylaxis in a subset of HAE-nC1INH.