Angioedema due to acquired C1-inhibitor deficiency without hematological condition: a multicenter French cohort study of 34 patients.

Background: Angioedema (AE) due to acquired C1-inhibitor deficiency (AAE-C1-INH) is a rare disease associating recurrent edema of 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 hematological condition METHODS: A multicenter retrospective cohort study of patients with AAE-C1-INH without hematological condition included from January 1999 to May 2024 in the French national CREAK registry; the clinical and biological characteristics of patients were detailed, then compared to 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; 26 (76%) displayed anti-C1-INH antibodies. After a median follow-up of 65 months, 4 (12%) patients were in spontaneous complete remission of angioedema; 15 (44%) were in complete response under long-term prophylactic treatment. Comparatively to 75 patients with lymphoma associated-AAE-C1-INH, patients with AAE-C1-INH without 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 AAE-C1-INH without hematological condition patients were similar to those of 30 monoclonal gammopathy associated-AAE-C1-INH patients.

Conclusion: AAE-C1-INH without hematological condition display 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 angioedema attacks among these patients.