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

Romain Stammler; Federica Defendi; Magali Aubineau; Beatrice Bibes; Isabelle Boccon-Gibod; Laurence Bouillet; Yoann Crabol; Marie Caroline Dalmas; Claire de Moreuil; Aurelien Delluc; Claire Dingremont; Aurelie Du-Thanh; Jerome Hadjadj; Pierre-Yves Jeandel; Galith Kalmi; Marion Lacoste; Ludovic Martin; Chloé Mc Avoy; Claire Blanchard-Delaunay; Marie Caroline Taquet; Olivier Fain; Delphine Gobert

doi:10.1016/j.jaip.2024.12.027

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

J Allergy Clin Immunol Pract. 2025 Jan 3:S2213-2198(24)01276-5. doi: 10.1016/j.jaip.2024.12.027. Online ahead of print.

Authors

Romain Stammler¹, Federica Defendi², Magali Aubineau³, Beatrice Bibes⁴, Isabelle Boccon-Gibod⁵, Laurence Bouillet⁵, Yoann Crabol⁶, Marie Caroline Dalmas⁷, Claire de Moreuil⁸, Aurelien Delluc⁹, Claire Dingremont¹⁰, Aurelie Du-Thanh¹¹, Jerome Hadjadj¹, Pierre-Yves Jeandel¹², Galith Kalmi¹, Marion Lacoste¹³, Ludovic Martin¹⁴, Chloé Mc Avoy¹, Claire Blanchard-Delaunay¹⁵, Marie Caroline Taquet⁷, Olivier Fain¹, Delphine Gobert¹⁶

Affiliations

¹ Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.
² Immunology department, Grenoble University Hospital, Grenoble, France.
³ Internal Medicine Department, Hospices Civils de Lyon, Lyons, France.
⁴ Internal Medicine Department, Saint Grégoire Hospital, Rennes, France.
⁵ French national reference center for angioedema (CREAK), Internal medicine department, Grenoble university hospital, Grenoble, France.
⁶ Internal medicine department, Vanne-Auray hospital center, Vanne, France.
⁷ Internal medicine, Strasbourg University Hospital center, Strasbourg, France.
⁸ Internal Medicine Department, La Cavale Blanche University Hospital, Brest, France; Department of Medicine, University of Ottawa, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada.
⁹ Internal Medicine Department, La Cavale Blanche University Hospital, Brest, France.
¹⁰ Internal medicine Department, Bigorre Hospital Center, Tarbes, France.
¹¹ Dermatology Department, Montpellier University Hospital, Montpellier, France.
¹² Internal medicine department, Hôpital Archet 1, Université Côte d'Azur, Nice, France.
¹³ Nephrology department, Centre hospitalier de la côte Basque, Bayonne, France.
¹⁴ Dermatology department, Angers University Hospital Center, Angers, France.
¹⁵ Internal medicine department, Niort Hospital Center, Niort, France.
¹⁶ Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France. Electronic address: delphine.gobert@aphp.fr.

PMID: 39756514
DOI: 10.1016/j.jaip.2024.12.027

Abstract

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.

Keywords: acquired angioedema; angioedema; autoimmune diseases; paraneoplastic syndrome.