Angioedema can be caused by either mast cell degranulation or activation of the
kallikrein-
kinin cascade. In the former case,
angioedema can be caused by
allergic reactions caused by
immunoglobulin E (
IgE)-mediated hypersensitivity to foods or drugs that can also result in acute
urticaria or a more generalized
anaphylactic reaction. Nonsteroidal anti-inflammatory drugs (
cyclooxygenase 1 inhibitors, in particular) may cause
angioedema with or without
urticaria, and
leukotrienes may have a particular role as a mediator of the swelling. Reactions to
contrast agents resemble
allergy with basophil and mast cell degranulation in the absence of specific
IgE antibody and can be generalized, that is, anaphylactoid.
Angioedema accompanies
chronic urticaria in 40% of patients, and approximately half have an autoimmune mechanism in which there is
IgG antibody directed to the subunit of the
IgE receptor (40%) or to
IgE itself (5%-10%).
Bradykinin is the mediator of
angioedema in
hereditary angioedema types I and II (C1 inhibitor [INH] deficiency) and the newly described type III disorder some of which are caused bya mutation involving
factor XII. Acquired C1 INH deficiency presents in a similar fashion to the hereditary disorder and is due either toC1 INH depletion by circulating
immune complexes or to an
IgG antibody directed to C1 INH. Although each of these causes excessive
bradykinin formation because of activation of the plasma
bradykinin-forming pathway, the
angioedema due to
angiotensin-converting enzyme inhibitors is caused by excessive
bradykinin levels due to inhibition of
bradykinin degradation. Idiopathic
angioedema (ie, pathogenesis unknown) may be histaminergic, that is, caused by mast cell degranulation with histamine release, or nonhistaminergic. The mediator pathways in the latter case are yet to be defined. A minority may be associated with the same
autoantibodies associated with
chronic urticaria.
Angioedema that is likely to be life threatening (
laryngeal edema or tongue/pharyngeal
edema that obstructs the airway) is seen in anaphylactic/
anaphylactoid reactions and the disorders mediated by
bradykinin.