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Multicenter Study
. 2025 Jan 21;219(1):uxae121.
doi: 10.1093/cei/uxae121.

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

Hadeil Morsi  1 , Aarnoud Huissoon  2 , Alexandros Grammatikos  3 , Andrew F Whyte  4 , Ania Manson  5 , Anjali Ekbote  2 , Anju Sivadasan  6 , Anne Pacita Rosillo Boulton  5 , Archana Herwadkar  7 , Ariharan Anantharachagan  8 , Arthur Price  6 , Cathal Steele  9 , Catherine Stroud  10 , Charu Chopra  11 , Dilani Arnold  12 , Efrem Eren  13 , Elizabeth Cleave  14 , Elizabeth Drewe  14 , Emily Moon  15 , Emily Zinser  16 , Grant Hayman  17 , Hana Alachkar  18 , Harichandana Ghanta  13 , Helen Bourne  10 , Intisar Abdelhakam  6 , John Dempster  19 , Katie Townsend  20 , Kavitha Sooriyakumar  2 , Lorena Lorenzo  20 , Magdalena Dziadzio  19 , Manisha Ahuja  10   21 , Maria Prasinou  22 , Marina Frleta-Gilchrist  23 , Michael Zhang  9 , Moira Thomas  23 , Pavaladurai Vijayadurai  8 , Prashantha Madhuri Vaitla  14 , Ravishankar Sargur  12 , Richard Herriot  24 , Robert L Yellon  5 , Sai Hurng Kham Murng  17 , Sara Drinkwater  15 , Sarah Denness  12 , Sarah Denman  25 , Shuayb Elkhalifa  26   27 , Sinisa Savic  25 , Sorena Kiani-Alikhan  22   28 , Tania I Coulter  9 , Tariq El-Shanawany  29 , Tasneem Rahman  17 , Tomaz Garcez  15 , Patrick F K Yong  16 , Rashmi Jain  1
Affiliations
Multicenter Study

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

Hadeil Morsi et al. Clin Exp Immunol. .

Abstract

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.

Keywords: MGUS; angioedema due to acquired C1 inhibitor deficiency; anti-C1 inhibitor autoantibodies; long-term prophylaxis; rituximab; splenic marginal zone lymphoma.

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Conflict of interest statement

A Manson received honoraria from CSL Behring, BioCryst, and Takeda for educational events and advisory boards. A Herwadkar received support for attending meetings from BioCryst, Pharming, and Takeda. E Cleave attended Takeda-sponsored management course (Amplify Rare) 2022. C Steele received advisory work and educational support from BioCryst, CSL Behring, Pharming, and Takeda. L Lorenzo received consulting, advisory work, and educational support from BioCryst, Pharming, and Takeda. M Dziadzio received support to attend educational meetings from CSL and Takeda. M Ahuja Received honoraria from BioCryst and Takeda for educational events and advisory boards. M Frleta-Gilchrist received support for attending a meeting from BioCryst. P Yong received consulting fees, honoraria, and/or support for attending meetings from Astria Therapeutics, BioCryst, CSL Behring, KalVista, Pharming, Pharvaris, and Takeda. S Elkhalifa received funds as part of an Advisory Board or expert consultation from BioCryst, CSL, and Takeda Pharmaceutical Companies, none of these funds related to this article. T El-Shanawany received educational support, research support, speaker fees, and/or consultant fees from ALK-Abello, Allergy Therapeutics, CSL, KalVista, Octapharma, Novartis, Takeda, and Viatris. T Garcez received consulting, advisory work, and educational support from BioCryst, CSL Behring, Novartis, Octapharma, Pharming, and Takeda. R Jain received educational support and advisory support from Takeda, Pharming, CSL Behring, and BioCryst. The rest of the authors do not have a conflict of interest to declare.

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