Angioedema Due to Acquired C1-Inhibitor Deficiency Without Hematological Condition: A Multicenter French Cohort Study of 34 Patients

Abstract

Background: Angioedema (AE) due to acquired C1-inhibitor deficiency (AAE-C1-INH) is a rare disease associating recurrent edema of the mucosa and skin. Several underlying diseases have been reported, mainly lymphoproliferative diseases and monoclonal gammopathy. However, 15% to 20% of patients never exhibit such a hematological condition.

Objective: To analyze specific features of patients with AAE-C1-INH without a hematological condition.

Methods: This is a multicenter, retrospective cohort study of patients with AAE-C1-INH without a hematological condition included from January 1999 to May 2024 in the French national CREAK (Centre de reference des angioedèmes à kinine) registry. The clinical and biological characteristics of patients were detailed and then compared with those of patients with AAE-C1-INH associated with lymphoid hemopathies or monoclonal gammopathy.

Results: Thirty-four patients were included. All patients displayed a functional C1-INH below 50% of the reference value, 26 (76%) also had a decreased C1-INH antigen level, and 26 (76%) displayed anti-C1-INH antibodies. After a median follow-up of 65 months, 4 (12%) patients were in spontaneous complete remission of AE; 15 (44%) were in complete response under long-term prophylactic treatment. Compared with 75 patients with lymphoma-associated AAE-C1-INH, patients with AAE-C1-INH without a hematological condition displayed a higher incidence of anti-C1-INH antibodies and received more frequently symptomatic or prophylactic treatment with a lower remission rate at last follow-up. Clinical and biological features of patients with AAE-C1-INH without a hematological condition were similar to those of 30 patients with monoclonal gammopathy-associated AAE-C1-INH.

Conclusions: AAE-C1-INH without a hematological condition displays a different clinical and biological presentation from lymphoma-associated AAE-C1-INH. No autoimmune disease was identified. Unlike rituximab, long-term prophylaxis seems to prevent AE attacks among these patients.

Keywords: Acquired angioedema; Angioedema; Autoimmune diseases; Paraneoplastic syndrome.