Hereditary Angioedema (HAE)
Inherited C1 esterase inhibitor deficiency with episodic angioedema; special considerations in pregnancy.
Hereditary angioedema (HAE) is an inherited condition characterized by
episodic swelling (edema) of the skin and/or mucous membranes. Swelling may involve the
face, extremities, genitals, gastrointestinal tract, and upper airways. Attacks may occur
spontaneously or be precipitated by trauma, medical or dental procedures, or other stressors.
HAE is most often caused by low levels (type I) or nonfunctional (type II)
C1 esterase inhibitor (C1-INH), a plasma protein that regulates the classical complement
pathway and inhibits several serine proteinases, including plasmin and kallikrein.
Uncontrolled activation of the classical complement pathway leads to consumption of C4 and
low serum C4 levels. Activation of kallikrein promotes excessive production of the
vasoactive peptide bradykinin, which in turn causes increased vascular permeability and
angioedema.
Observational data suggest that women with hereditary angioedema may experience increased
attack rates during pregnancy, particularly involving the gastrointestinal tract, followed
by extremity and facial edema. Attacks involving the urogenital region appear to be less
common, and laryngeal attacks are reported as rare in some series. C1-INH concentrate can
be used to treat acute attacks during pregnancy and is reported to be safe for both mother
and fetus.
Some experts recommend that patients with frequent or severe HAE episodes receive
C1-INH concentrate prophylaxis to cover labor and delivery. Regional anesthesia (for example,
epidural anesthesia) is not generally considered contraindicated solely due to HAE, but
careful coordination with anesthesia and allergy/immunology teams is advised. Rarely,
maternal death related to HAE has been reported.
References
-
Hereditary Angioedema (HAE). Online Mendelian Inheritance in Man (OMIM) entry 106100.
Available at:
http://www.omim.org/entry/106100.
-
Martinez-Saguer I, et al. Characterization of acute hereditary angioedema attacks during
pregnancy and breast-feeding and their treatment with C1 inhibitor concentrate.
Am J Obstet Gynecol. 2010;203(2):131.e1–7. PMID:
20471627.
-
Bowen T, et al. 2010 International consensus algorithm for the diagnosis, therapy and
management of hereditary angioedema. Allergy Asthma Clin Immunol.
2010;6(1):24. PMID:
20667127.
-
Bouillet L. Hereditary angioedema in women. Allergy Asthma Clin Immunol.
2010;6(1):17. PMID:
20667120.
-
Postnikoff IM, Pritzker KP. Hereditary angioneurotic edema: an unusual case of maternal
mortality. J Forensic Sci. 1979;24(2):473–478. PMID:
541623.
