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

ABSTRACTAngioedema 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.