Camila Lopes Veronez1,2, Anete Sevciovic Grumach3. 1. Department of Medicine, Division of Rheumatology, Allergy and Immunology, University of California San Diego. 2. Research Service, San Diego Veterans Affairs Healthcare, San Diego, California, USA. 3. Clinical Immunology, Faculdade de Medicina, University Center Health ABC, Santo Andre, Sao Paulo, Brazil.
Abstract
PURPOSE OF REVIEW: Angioedema without urticaria is composed of an increasing subtype's variety and presents a challenging diagnosis. This review summarizes the subtypes recently described and subsequent new findings helpful within their classification. RECENT FINDINGS: New methods to measure cleaved high molecular weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Three new subtypes of hereditary angioedema (HAE) with normal C1 inhibitor were described in the past two years: HAE due to mutation in plasminogen gene, in kininogen gene, and in angiopoietin-1 gene; implicating the fibrinolytic and contact systems, and the regulation of vasculature, respectively. The understanding of some mechanisms in angioedema has been improved, compatible to the dominant-negative for some C1 inhibitor variants; furthermore, the increased activation of truncated F12 mutants by plasma kallikrein; and the diminished binding of angiopoietin-1 to its receptor. SUMMARY: The validation of biomarkers for the contact system activation could be beneficial in differentiating bradykinin - from histaminergic-mediated angioedema. Currently, the available laboratorial tests are still somewhat restricted to the evaluation of the complement activation and the mediators of nonhistaminergic and nonbradykinin-mediated angioedema remain to be identified.
PURPOSE OF REVIEW: Angioedema without urticaria is composed of an increasing subtype's variety and presents a challenging diagnosis. This review summarizes the subtypes recently described and subsequent new findings helpful within their classification. RECENT FINDINGS: New methods to measure cleaved high molecular weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Three new subtypes of hereditary angioedema (HAE) with normal C1 inhibitor were described in the past two years: HAE due to mutation in plasminogen gene, in kininogen gene, and in angiopoietin-1 gene; implicating the fibrinolytic and contact systems, and the regulation of vasculature, respectively. The understanding of some mechanisms in angioedema has been improved, compatible to the dominant-negative for some C1 inhibitor variants; furthermore, the increased activation of truncated F12 mutants by plasma kallikrein; and the diminished binding of angiopoietin-1 to its receptor. SUMMARY: The validation of biomarkers for the contact system activation could be beneficial in differentiating bradykinin - from histaminergic-mediated angioedema. Currently, the available laboratorial tests are still somewhat restricted to the evaluation of the complement activation and the mediators of nonhistaminergic and nonbradykinin-mediated angioedema remain to be identified.
Authors: Marcel Gutierrez; Camila L Veronez; Solange O Rodrigues Valle; Rozana Fátima Gonçalves; Mariana Paes Leme Ferriani; Adriana S Moreno; L Karla Arruda; Marcelo Vivolo Aun; Pedro Giavina-Bianchi; Maria Luiza Oliva Alonso; Joao B Pesquero; Anete S Grumach Journal: Clin Rev Allergy Immunol Date: 2021-03-23 Impact factor: 8.667