Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional
C1 esterase inhibitor (C1-INH).
Acquired angioedema (AAE) is caused by either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and AAE can be life-threatening. The screening test for both conditions is
complement component C4, which is low to absent at times of
angioedema or during quiescent periods. A useful test to differentiate HAE from AAE is C1q
protein, which is normal in HAE and low in AAE. There are three types of HAE: type 1 HAE is most common, occurring in ∼85% of patients and characterized by decreased production of C1-INH, resulting in reduced functional activity to 5-30% of normal. In type 2, which occurs in 15% of cases, C1-INH is detectable in normal or elevated quantities but is dysfunctional. Finally, type 3, which is rare and almost exclusively occurs in women, is
estrogen dependent and associated with normal CI-INH and C4 levels. One-third of these patients have a gain-of-function mutation in
clotting factor XII leading to
kallikrein-driven
bradykinin production. Although the
anabolic steroid,
danazol, is useful in increasing the concentration of C4 and reducing the episodes of
angioedema in HAE and AAE, it has expected adverse effects. Fortunately, disease-specific
therapies are available and include C1-INH
enzyme for i.v. infusion either acutely or empirically,
ecallantide, an inhibitor of
kallikrein, and
icatibant, a
bradykinin B2-receptor antagonist, both approved for acute
angioedema and administered, subcutaneously.