Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)-A Bicenter Retrospective Study on Diagnosis, Course, and Therapy

Susanne Trainotti; Felix Johnson; Janina Hahn; Benedikt Hofauer; Jens Greve; Barbara Wollenberg; Thomas K Hoffmann; Robin Lochbaum

doi:10.1016/j.jaip.2023.09.003

Acquired Angioedema Due to C1-Inhibitor Deficiency (AAE-C1-INH)-A Bicenter Retrospective Study on Diagnosis, Course, and Therapy

J Allergy Clin Immunol Pract. 2023 Dec;11(12):3772-3779. doi: 10.1016/j.jaip.2023.09.003. Epub 2023 Sep 15.

Authors

Susanne Trainotti¹, Felix Johnson², Janina Hahn³, Benedikt Hofauer², Jens Greve³, Barbara Wollenberg⁴, Thomas K Hoffmann³, Robin Lochbaum³

Affiliations

¹ Department of Otorhinolaryngology, Technical University of Munich, Munich, Germany. Electronic address: susanne.trainotti@tum.de.
² University Hospital for Otorhinolaryngology, Head and Neck Surgery, Medical University of Innsbruck, Innsbruck, Austria.
³ Department of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, Germany.
⁴ Department of Otorhinolaryngology, Technical University of Munich, Munich, Germany.

PMID: 37716525
DOI: 10.1016/j.jaip.2023.09.003

Abstract

Background: Acquired angioedema with C1-inhibitor deficiency (AAE-C1-INH) is a rare condition resembling hereditary angioedema (HAE), but with late onset and low C1-inhibitor (C1-INH) due to consumption potentially caused by autoimmune diseases and mainly lymphatic malignancies. Being about 10-fold rarer than HAE, there is limited knowledge and no licensed therapy.

Objective: To report clinical and biological data from a newly described population of 20 patients with AAE-C1-INH assessing diagnostic delay, AAE-C1-INH:HAE-ratio, underlying conditions, and therapeutic management in Germany.

Methods: Retrospective data analysis of 20 patients from 2 angioedema centers in southern Germany.

Results: Median age at symptoms' onset was 64 years (60% females), with predominant swellings of the face (85%) and low levels for C1-INH in almost all patients. The ratio AAE-C1-INH:HAE was 1:9.7. From symptoms' onset to diagnosis of AAE-C1-INH, the median delay was 7.5 months, and between AAE-C1-INH symptoms' onset and diagnosis of the underlying hematological condition (n = 9) it was 4 months (median). Four patients had a history of solid neoplasm, 1 had a papillary thyroid carcinoma as the only potential cause for AAE-C1-INH, with treatment of the malignancy resulting in resolution of AAE-C1-INH. All the symptomatic patients were treated with off-label on-demand icatibant subcutaneously or C1-INH concentrate intravenously, and 6 severely affected patients needed off-label long-term prophylaxis with good symptom control.

Conclusions: AAE-C1-INH is characterized by late-onset swellings mainly involving the face and low C1-INH levels. Diagnostic delay for AAE-C1-INH is further decreasing despite being about 10-fold rarer than HAE. Patients severely affected without underlying condition or no indication for treatment could benefit from off-label therapy.

Keywords: Acquired angioedema; Angioedema; C1 inhibitor protein; Lymphoproliferative disorders; Papillary; Thyroid cancer.

MeSH terms

Angioedema* / drug therapy
Angioedemas, Hereditary* / diagnosis
Angioedemas, Hereditary* / drug therapy
Complement C1 Inhibitor Protein / therapeutic use
Delayed Diagnosis / adverse effects
Female
Humans
Male
Middle Aged
Retrospective Studies

Substances

Complement C1 Inhibitor Protein
SERPING1 protein, human

Supplementary concepts

Acquired angioedema