A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency

Background: Acquired angioedema due to C1-inhibitor deficiency (AAE-C1-INH) is very rare compared to its prototype, hereditary angioedema. An updated characterization of the AAE-C1-INH cohort in the UK is required to inform management. Objectives: To describe the disease burden of AAE-C1-INH, long-term prophylaxis (LTP) and the clinical, immunochemical, and treatment profiles of AAE-associated diseases in the UK. Method: Retrospective data on 117 AAE-C1-INH patients were collected using a national survey proforma across 25/34 Adult Clinical Immunology and Allergy centres in the UK. Other European cohorts were compared. Results: The median age at AAE-C1-INH diagnosis was 65 years with 3.4% of patients diagnosed below 40 years. The median delay in diagnosis was 1 year. Antifibrinolytics and attenuated androgens showed comparable efficacy to LTP, at 88.9% and 89.5%, respectively. A haematological disorder was identified in 83.8% of AAE-C1-INH patients compared to 3.4% of autoimmune diseases. The predominant haematological disorders were splenic marginal zone lymphoma 34% followed by MGUS 16%. The severity of angioedema did not depend on the associated disease. Anti-C1INH-autoantibodies testing was limited to 23.1%. Rituximab monotherapy was effective in treating 9/9 splenic marginal zone lymphoma and 1/2 MGUS-associated AAE-C1-INH. Rituximab efficacy was independent of anti-C1INH-autoantibodies detection with response in 3/3 seronegative and 4/4 seropositive patients. Conclusion: The diagnosis of AAE-C1-INH should not be overlooked below the age of 40 years. The choice of oral LTP should be informed by the propensity to side effects. B cell depletion could be considered in treating monoclonal B cell disorder-associated-AAE-C1-INH in the absence of haematological indications. Further studies are required to address the clinical utility of anti-C1INH-autoantibodies.

Citation

Morsi H, Huissoon A, Grammatikos A, Whyte AF, Manson A, Ekbote A, Sivadasan A, Boulton APR, Herwadkar A, Anantharachagan A, Price A, Steele C, Stroud C, Chopra C, Arnold D, Eren E, Cleave E, Drewe E, Moon E, Zinser E, Hayman G, Alachkar H, Ghanta H, Bourne H, Abdelhakam I, Dempster J, Townsend K, Sooriyakumar K, Lorenzo L, Dziadzio M, Ahuja M, Prasinou M, Frleta-Gilchrist M, Zhang M, Thomas M, Vijayadurai P, Vaitla PM, Sargur R, Herriot R, Yellon RL, Murng SHK, Drinkwater S, Denness S, Denman S, Elkhalifa S, Savic S, Kiani-Alikhan S, Coulter TI, El-Shanawany T, Rahman T, Garcez T, Yong PFK, Jain R. A multi-centre UK-based survey on angioedema secondary to acquired C1 inhibitor deficiency. Clin Exp Immunol. 2025 Jan 21;219(1):uxae121. doi: 10.1093/cei/uxae121.

Type

Article