Evaluation of a patient with symptoms suggestive of hereditary angioedema (HAE) and NORMAL complement studies

ACE: angiotensin-converting enzyme; ARB: angiotensin receptor blocker; C1-INH: C1 esterase inhibitor; C4: complement factor 4; DPP-4: dipeptidyl peptidase 4; HAE: hereditary angioedema; NSAID: nonsteroidal antiinflammatory drug.

* Known HAE-specific mutations include variants in the genes for factor XII, angiopoietin 1, plasminogen 1, kininogen 1, myoferlin, and heparan sulfate-glucosamine 3-O-sulfotransferase 6.

¶ It may take several months to see the impact of discontinuation of ACE inhibitors. Also, note that ACE inhibitors can "unmask" underlying angioedema disorders, so patients can have HAE with normal C1-INH that is exacerbated by ACE inhibitors. Reconsider this possibility if future angioedema episodes occur. ARBs are a very rare cause of angioedema but are tolerated by most patients with ACE inhibitor-induced angioedema. Discontinuation of estrogens or NSAIDs should have a relatively rapid impact.

Δ Discussions of dosing and duration of antihistamines, montelukast, and omalizumab are found in the UpToDate topic on HAE with normal C1-INH.

◊ Low C1-INH protein levels with normal C4 are usually due to laboratory error. Repeat. Low C4 with normal C1-INH can be from inherited C4 deficiency or other diseases (eg, lupus).