Fig. 1

Mechanisms of angioedema [2, 6,7,8]. A Histamine induced. Upon exposure to an allergen, it is taken up by antigen-presenting cells (e.g. dendritic cells) and proteolyzed to produce small peptides. These peptides are then presented with major histocompatibility (MHC) class II antigen as a complex on the cell surface and recognised by T-helper (Th) lymphocyte receptors. This leads to the activation of T cells and release of Th2 cytokines that promote the differentiation of B cells to plasma cells and the production of specific IgE antibodies that recognise the original antigen. These antibodies bind to high-affinity IgE receptor FcεRI on mast cells and persist for weeks, months or years. Upon re-exposure to the allergen, the allergenic peptide is recognised by these bound IgEs, activating the mast cells to release bioactive mediators such as histamine. Binding of histamine on selective receptors of the vascular endothelium causes vasodilation and increased permeability. Mast cells can also be activated and triggered to produce histamine mediators through non-IgE-mediated response. B Bradykinin-induced. The contact pathway is initiated when factor XII (or Hageman factor) binds to damaged tissue and converts to factor XIIa, which then converts prekallikrein to plasma kallikrein. Finally, kallikrein cleaves HMWK to form bradykinin, which binds B2 receptors on the vascular endothelium, triggering vasodilation and increased permeability. Plasmin from the fibrinolytic system can convert factor XII into factor XIIa, accelerating the bradykinin production from HMWK. Multiple biological and pharmacological inhibitors can be used to treat bradykinin-induced angioedema. C1-INH can act on multiple stages of the contact and fibrinolytic system to inhibit the production of bradykinin. Ecallantide is a kallikrein inhibitor that blocks the cleavage of HMWK into bradykinin, and icatibant is an antagonist that prevents bradykinin from binding to its receptor