Background: Angiotensin-converting enzyme inhibitor–associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. Methods: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. Results: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEI-AAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. Conclusions: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Angiotensin-converting enzyme inhibitor– associated angioedema: From bed to bench / Carucci, L.; Bova, M.; Petraroli, A.; Ferrara, A. L.; Sutic, A.; de Crescenzo, G.; Cordisco, G.; Margaglione, M.; Gambardella, J.; Spadaro, G.; Genovese, A.; Loffredo, S.. - In: JOURNAL OF INVESTIGATIONAL ALLERGOLOGY & CLINICAL IMMUNOLOGY. - ISSN 1018-9068. - 30:4(2020), pp. 272-280. [10.18176/jiaci.0458]

Angiotensin-converting enzyme inhibitor– associated angioedema: From bed to bench

Ferrara A. L.;de Crescenzo G.;Gambardella J.;Spadaro G.;Loffredo S.
2020

Abstract

Background: Angiotensin-converting enzyme inhibitor–associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. Methods: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. Results: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEI-AAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. Conclusions: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.
2020
Angiotensin-converting enzyme inhibitor– associated angioedema: From bed to bench / Carucci, L.; Bova, M.; Petraroli, A.; Ferrara, A. L.; Sutic, A.; de Crescenzo, G.; Cordisco, G.; Margaglione, M.; Gambardella, J.; Spadaro, G.; Genovese, A.; Loffredo, S.. - In: JOURNAL OF INVESTIGATIONAL ALLERGOLOGY & CLINICAL IMMUNOLOGY. - ISSN 1018-9068. - 30:4(2020), pp. 272-280. [10.18176/jiaci.0458]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/887298
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