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

C1INH deficiency angioedema monoclonal gammopathies

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
30 Sep 2024
Historique:
received: 26 04 2024
revised: 26 08 2024
accepted: 13 09 2024
medline: 3 10 2024
pubmed: 3 10 2024
entrez: 2 10 2024
Statut: aheadofprint

Résumé

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.

Sections du résumé

BACKGROUND BACKGROUND
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.
OBJECTIVE OBJECTIVE
Describe the biological and clinical characteristics, evolution and response to treatment of MGUS-associated AAE-C1-INH.
MATERIAL AND METHODS METHODS
We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period.
RESULTS RESULTS
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.
CONCLUSION CONCLUSIONS
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.

Identifiants

pubmed: 39357560
pii: S2213-2198(24)00942-5
doi: 10.1016/j.jaip.2024.09.016
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Constance Lahuna (C)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Federica Defendi (F)

Immunology Laboratory, University Hospital, Grenoble, France.

Laurence Bouillet (L)

French national reference center for angioedema (CREAK), Internal medicine department, Grenoble university hospital, France; University Grenoble Alpes, CNRS, UMR 5525, VetAgro Sup, Grenoble INP, CHU Grenoble Alpes, TIMC, 38000 Grenoble, France Internal Medicine department, University Hospital La, Tronche, France.

Isabelle Boccon-Gibod (I)

French national reference center for angioedema (CREAK), Internal medicine department, Grenoble university hospital, France.

Arsene Mekinian (A)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Paul Coppo (P)

Sorbonne Université, Hematology Department, AP-HP, Hôpital Saint Antoine, F-75012 Paris.

Henri Adamski (H)

Dermatology Department, Pontchaillou University Hospital, Rennes, France.

Stephanie Amarger (S)

Dermatology Department, University Hospital, Clermont Ferrand, France.

Guillaume Armengol (G)

Internal Medicine Department, Charles Nicolle University Hospital, Rouen, France.

Magali Aubineau (M)

Internal Medicine Department, Hospices Civils de Lyon, France.

Beatrice Bibes (B)

Internal Medicine Department, Saint Grégoire Hospital, Rennes, France.

Claire Blanchard-Delaunay (C)

Internal Medicine Department, Georges Renons Hospital, Niort, France.

Gilles Blaison (G)

Internal Medicine Department, Louis Pasteur Hospital, Colmar, France.

Benoit Brihaye (B)

Internal Medicine Department, Hospital, Saint Quentin, France.

Pascal Cathebras (P)

Internal Medicine Department, University Hospital, St Etienne, France.

Olivier Caubet (O)

Internal Medicine Department, Hospital, Libourne, France.

Claire Demoreuil (C)

Internal Medicine Department, Brest University Hospital, Brest, France.

Julien Desblache (J)

Internal Medicine Department, Hospital, Pau, France.

Francois Durupt (F)

Dermatology Department, Du Parc Clinic, Lyon, France.

Stephane Gayet (S)

Internal Medicine Department, La Timone University Hospital, Assistance publique-Hôpitaux de, Marseille, France.

Guillaume Gondran (G)

Internal Medicine Department, Dupuytren University Hospital, Limoges, France.

Jerome Hadjadj (J)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Galith Kalmi (G)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Gisele Kanny (G)

Internal Medicine, Clinical Immunology Department, University Hospital, Nancy, France.

Marion Lacoste (M)

Internal Medicine Department, Hospital, Troyes, France.

David Launay (D)

Internal and immunological Medicine department, Lille Hospital, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille university, F-59000 Lille, France, Inserm, F-59000 Lille, France.

Kim Heang Ly (KH)

Internal Medicine Department, Dupuytren University Hospital, Limoges, France.

Chloé McAvoy (C)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Ludovic Martin (L)

Dermatology Department, University Hospital, Angers.

Yann Ollivier (Y)

Medicine Department, Cote de Nacre University Hospital, Caen, France.

Fabien Pelletier (F)

Dermatology Department, Allergology Center, Besançon University Hospital, Besançon, France.

Aylsa Robbins (A)

Internal Medicine Department, University Hospital, Reims.

Damien Roos-Weil (D)

Sorbonne Université, Hematology Department, Pitié Salpêtrière Hospital, Paris APHP, France.

Olivier Fain (O)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France.

Delphine Gobert (D)

Sorbonne Université, service de médecine interne, AP-HP, Hôpital Saint Antoine, F-75012 Paris, France. Electronic address: delphine.gobert@aphp.fr.

Classifications MeSH