Angioedema without urticaria: novel findings which must be measured in clinical setting

Curr Opin Allergy Clin Immunol. 2020 Jun;20(3):253-260. doi: 10.1097/ACI.0000000000000633.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angioedemas, Hereditary / diagnosis*
  • Angioedemas, Hereditary / genetics
  • Angioedemas, Hereditary / immunology
  • Angiopoietin-1 / genetics
  • Biomarkers
  • Complement Activation / genetics*
  • Diagnosis, Differential
  • Humans
  • Kininogens / genetics
  • Mutation
  • Plasminogen / genetics

Substances

  • ANGPT1 protein, human
  • Angiopoietin-1
  • Biomarkers
  • KNG1 protein, human
  • Kininogens
  • Plasminogen