Return to content in this issue


Angiotensin-converting enzyme inhibitor-associated angioedema in a cohort of Caucasian patients: from bed to bench

Carucci L1, Bova M2, Petraroli A2, Ferrara AL2, Sutic A3, de Crescenzo G4, Cordisco G5, Margaglione M5, Gambardella J6, Spadaro G1,2, Genovese A1-2, Loffredo S2,7

1Post-Graduate Program in Clinical Immunology and Allergy, University of Naples Federico II, Naples, Italy.
2Department of Translational Medical Sciences and Interdepartmental Center for Research in Basic and Clinical Immunology Sciences, University of Naples Federico II, Naples, Italy.
3Division of Clinical Immunology, Allergology and Rheumatology, Department of Internal Medicine, University of Zagreb School of Medicine, University Hospital Dubrava, Zagreb, Croatia.
4Division of Clinical Immunology and Allergy, Sant’Anna and San Sebastiano Hospital, Caserta, Italy.
5Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
6Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
7Institute of Experimental Endocrinology and Oncology G. Salvatore, National Research Council, Naples, Italy

J Investig Allergol Clin Immunol 2020; Vol. 30(4)
doi: 10.18176/jiaci.0458

Background: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) occurs in 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 phospholipases A2 (sPLA2) in ACEI-AAE pathogenesis.
Methods: The clinical and laboratory data of ACEI-AAE patients were collected from two angioedema centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare concentrations of laboratory parameters. Genetic analyses to detect mutations in SERPING1, ANGPT1, PLG, and F12 genes were performed in a subset of patients.
Results: 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to symptom onset from the start of ACEI therapy was 3 years (range 30 days-20 years). The most commonly affected sites were 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 were not modified. No mutations were detected in the genes analyzed.
Conclusions: Our data suggest that sartans can be 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 ACEI-AAE pathogenesis.

Key words: Angiotensin-Converting Enzyme Inhibitor, Angioedema, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factor A, Phospholipases A2, Genetic analysis, C1-inhibitor, Biomarkers