Angioedema due to acquired C1-inhibitor deficiency associated with monoclonal gammopathies of undetermined significance

• Published in: The journal of allergy and clinical immunology in practice (Cambridge, MA)
• Main Authors: Lahuna, Constance, Defendi, Federica, Bouillet, Laurence, Boccon-Gibod, Isabelle, Mekinian, Arsene, Coppo, Paul, Adamski, Henri, Amarger, Stephanie, Armengol, Guillaume, Aubineau, Magali, Bibes, Beatrice, Blanchard-Delaunay, Claire, Blaison, Gilles, Brihaye, Benoit, Cathebras, Pascal, Caubet, Olivier, Demoreuil, Claire, Desblache, Julien, Durupt, Francois, Gayet, Stephane, Gondran, Guillaume, Hadjadj, Jerome, Kalmi, Galith, Kanny, Gisele, Lacoste, Marion, Launay, David, Ly, Kim Heang, McAvoy, Chloé, Martin, Ludovic, Ollivier, Yann, Pelletier, Fabien, Robbins, Aylsa, Roos-Weil, Damien, Fain, Olivier, Gobert, Delphine
• Format: Journal Article
• Language: English
• Published: United States 30-09-2024
• Subjects: angioedema; C1INH deficiency; monoclonal gammopathies
• ISSN: 2213-2201

No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet.
Describe the biological and clinical characteristics, evolution and response to treatment of MGUS-associated AAE-C1-INH.
We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period.
Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11 and IgA in 6 patients. Mean age at first angioedema attack was 63 years (SD = 13) and at diagnosis 66 years (SD = 11). 88 % of patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. 50 % of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of which 60% had an undetectable serum monoclonal immunoglobulin.
Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attacks frequency increases.