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To the Editor: I read with great interest the article by Vanderschueren et al1 in the September 2009 issue of Mayo Clinic Proceedings regarding monoclonal gammopathy of undetermined significance. The first case provided an excellent overview of the acquired form of angioedema. However, the authors were incorrect in their discussion of the treatment of this disease. It is correct that the first goal is to treat the underlying disorder. The second goal is long-term prophylaxis of acute attacks. This is most commonly achieved with antifibrinolytic agents such as tranexamic acid.
I disagree with their discourse on the medical management of acute attacks. Although the US Food and Drug Administration (FDA) has not approved medications for the indication of acute attacks of acquired angioedema, treatments are available. The preferred treatment is replacement of C1 inhibitor (C1-INH). This can be accomplished by giving either fresh frozen plasma or C1-INH concentrate. There has been a theoretical concern that fresh frozen plasma contains some of the substances, such as C4, that could potentially worsen the clinical course. However, this concern has not been substantiated clinically.2 Cinryze (ViroPharma, Exton, PA), a C1-INH concentrate, was recently approved by the FDA for use in prophylactic treatment of hereditary angioedema (HAE).3 Berinert P (CSL Behring, Marburg, Germany) is another form of C1-INH concentrate that has been available in some European countries for many years. It has an excellent track record for both prophylaxis and treatment of acute attacks.4 Because acquired angioedema is often the result of hypercatabolism of C1-INH, one can assume that the dosing required for treatment of hypercatabolism would be higher than that for HAE.
Other, much-needed therapeutic options are on the horizon. DX-88 (Ecallantide, Dyax, Cambridge, MA) is a plasma kallikrein inhibitor, and full FDA approval is pending. The mechanism of this medication is to prevent the formation of bradykinin via the kallikrein-kinin system, which is normally inhibited by C1-INH.3 Icatibant (Jerini, Berlin, Germany) is a synthetic decapeptide structurally similar to bradykinin that functions as a specific inhibitor to the bradykinin B2 receptor, thus preventing the clinical picture of angioedema. Despite excellent initial study results, the medication was rejected by the FDA for acute attacks of HAE and is currently undergoing additional investigation.
Angioedema in all its forms is a complex disease process. The clinician must have a detailed understanding of its pathophysiology to appreciate the treatment options.