An Atypical Case of Angioedema With Normal C1-Inhibitor Responding to Both C1-Inhibitor Concentrate and Omalizumab

Abstract

Angioedema is classified into mast cell-mediated and bradykinin-mediated types. Mast cell-mediated angioedema (AE-MC) frequently presents with wheals and may respond to antihistamines and/or corticosteroids. In contrast, bradykinin-mediated angioedema (AE-BK) neither accompanies urticaria nor responds to these treatments, but may respond to medications targeting bradykinin or molecules involved in its production pathway. Hereditary angioedema (HAE), a subtype of AE-BK, includes a small population of HAE that exhibit normal C1 inhibitor (C1-INH) levels, classified as HAE with normal C1-INH (HAE-nC1INH). However, genetic abnormalities are not identified in most cases, complicating the differentiation from AE-MC. We present a case of a 41-year-old woman with recurrent gastrointestinal edema with abdominal pain, and marked swelling of the abdomen and extremities without C1-INH deficiency. Neither family history nor genetic mutations were identified; however, her symptoms, including the lack of urticaria, and resistance to antihistamines and corticosteroids were consistent with AE-BK. Considering the possibility of AE-BK including HAE-nC1INH, she received intravenous plasma-derived C1-INH (pdC1-INH) from Day 112 (with Day 0 as her first visit) when an attack occurred, resulting in a substantial reduction of symptom severity. From Day 266, she was treated with q4w 300 mg omalizumab and her attack-related symptoms largely reduced throughout the course without further administrations of pdC1-INH. This case suggests a certain level of overlap between AE-BK and AE-MC, and the importance of trying anti-immunoglobulin E medications for refractory angioedema.