Abstract
The aim of treatment of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (HAE-C1-INH) is either treating acute attacks or preventing attacks by using prophylactic treatment. For treating acute attacks, plasma-derived C1 inhibitor (C1-INH) concentrates, a bradykinin B2 receptor antagonist, and a recombinant human C1-INH are available in Europe. In the United States, a plasma-derived C1-INH concentrate, a bradykinin B2 receptor antagonist, and a plasma kallikrein inhibitor have been approved. Fresh frozen plasma is also available for treating acute attacks. Short-term prophylactic treatment focuses on C1-INH and attenuated androgens. Long-term prophylactic treatments include attenuated androgens such as danazol, stanozolol, and oxandrolone, antifibrinolytics, and a plasma-derived C1-INH concentrate. Plasma-derived C1-INH and a bradykinin B2 receptor antagonist are permitted for self-administration and home therapy. The number of management options has increased considerably within the last few years, thus helping to diminish the burden of HAE.
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Gösswein T, Kocot A, Emmert G, et al. Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet Genome Res. 2008;121:181–8.
Pappalardo E, Caccia S, Suffritti C, et al. Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol. 2008;45:3536–44.
Davis 3rd AE. Hereditary angioedema: a current state-of-the-art review, III: mechanisms of hereditary angioedema. Ann Allergy Asthma Immunol. 2008;100:S7–12.
Bork K, Barnstedt SE, Koch P, et al. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000;356:213–7.
Dewald G, Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor. Biochem Biophys Res Commun. 2006;343:1286–9.
Bork K, Wulff K, Hardt J, et al. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol. 2009;124:129–34.
Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000;75:349–54.
Bork K, Barnstedt SE. Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema. J Am Dent Assoc. 2003;134:1088–94.
Brackertz D, Kueppers F. Hereditary angioneurotic oedema. Lancet. 1973;2:680.
Bork K, Barnstedt SE. Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with hereditary angioedema. Arch Intern Med. 2001;161:714–8.
Bork K, Meng G, Staubach P, et al. Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema. Transfusion. 2005;45:1774–84.
Bork K, Staubach P, Hardt J. Treatment of skin swellings with C1-inhibitor concentrate in patients with hereditary angio-oedema. Allergy. 2008;63:751–7.
•• Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124:801–8. This article reported the results of a randomized, placebo-controlled clinical trial with C1-INH concentrate in hereditary angioedema.
Craig TJ, Wasserman RL, Levy RJ, et al. Prospective study of rapid relief provided by C1 esterase inhibitor in emergency treatment of acute laryngeal attacks in hereditary angioedema. J Clin Immunol. 2010;30:823–9.
Wasserman RL, Levy RJ, Bewtra AK, et al. Prospective study of C1 esterase inhibitor in the treatment of successive acute abdominal and facial hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2011;106:62–8.
Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med. 1996;334:1630–4.
Farkas H, Jakab L, Temesszentandrasi G. Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy. J Allergy Clin Immunol. 2007;120:941–7.
www.awmf.org/leitlinien/detail/ll/061-029.html Accessed April 24, 2012
Levi M, Choi G, Picavet C, et al. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol. 2006;117:904–8.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001207/human_med_001448.jsp&mid=WC0b01ac058001d124 Product information. EPAR. Accessed April 21, 2012
Hock FJ, Wirth K, Albus U, et al. Hoe 140 a new potent and long acting bradykinin-antagonist: in vitro studies. Br J Pharmacol. 1991;102:769–73.
Marceau F, Regoli D. Bradykinin receptor ligands: therapeutic perspectives. Nat Rev Drug Discov. 2004;3:845–52.
Bork K, Yasothan U, Kirkpatrick P. Icatibant. Nat Rev Drug Discov. 2008;7:801–2.
Wirth K, Hock FJ, Albus U, et al. Hoe 140 a new potent and long acting bradykinin-antagonist: in vivo studies. Br J Pharmacol. 1991;102:774–7.
Bork K, Frank J, Grundt B, et al. Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (Icatibant). J Allergy Clin Immunol. 2007;119:1497–503.
•• Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363:532–41. This article provides information about the results of the first randomized, controlled clinical study of icatibant in hereditary angioedema.
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000899/human_med_000793.jsp&murl=menus/medicines/medicines.jsp&mid=WC0b01ac058001d124 . Product information. EPAR. Annex 1. Accessed April 21, 2012
Lumry WR, Li HH, Levy RJ. Randomized placebo-controlled trial of the bradykinin B receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011;107:529–37.
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM260022.pdf. Accessed April 21, 2012
Aberer W, Toubi E (2011) Safety, tolerability and efficacy of self-administered icatibant for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol 107:pp A1-A138, A112, P337
Boccon-Gibod I, Bouillet L. Safety and efficacy of icatibant self-administration for acute hereditary angioedema. Clin Exp Immunol. 2012;168:303–7.
Levy RJ, Lumry WR, McNeil DL, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104:523–9.
•• Cicardi M, Levy RJ, McNeil DL. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363:523–31. This article provides information about the outcome of a Phase III study concerning safety and efficacy of ecallantide in hereditary angioedema.
Stolz LE, Sheffer AL. Prospective, double-blind, placebo-controlled trials of ecallantide for acute attacks of hereditary angioedema. Expert Rev Clin Immunol. 2012;8:25–32.
Beck TR, Baird LG. Anaphylactic reaction and antibodies to DX-88 (kallikrein inhibitor) in a patient with hereditary angioedema (response). J Allergy Clin Immunol. 2006;117:477.
Caballero T, Lopez-Serrano C. Anaphylactic reaction and antibodies to DX-88 (kallikrein inhibitor) in a patient with hereditary angioedema. J Allergy Clin Immunol. 2006;117:476–77. discussion 477.
www.fda.gov/downloads/…/ucm170334.pdf, Accessed April 21, 2012
•• Zuraw B, Cicardi M, Levy RJ, et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010;126(821-827):e814. This article reported Phase III study data on the efficacy and safety of rhC1-INH in treating HAE attacks.
Relan A, Haase G, Hack E, et al. Dose justification for recombinant human C1INH for the treatment of acute angioedema attacks in patients with hereditary angioedema. Allergy. 2010;65:445–6.
Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100:153–61.
Sheffer AL, Austen KF, Rosen FS. Tranexamic acid therapy in hereditary angioneurotic edema. N Engl J Med. 1972;287:452–4.
•• Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363:513–22. This article provides information about the study data for the efficacy and safety of a nanofiltered C1-INH concentrate for both acute and long-term prophylactic treatment of hereditary angioedema.
Bork K, Witzke G. Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. J Allergy Clin Immunol. 1989;83:677–82.
Tallroth GA. Long-term prophylaxis of hereditary angioedema with a pasteurized C1 inhibitor concentrate. Int Arch Allergy Immunol. 2011;154:356–9.
Martinez-Saguer I, Heller C, Fischer D, et al. Prophylactic treatment with pasteurised C1 inhibitor in hereditary angioedema (HAE) - a prospective 32 months follow up. Blood. 1999;94(10):2339. Sup 1, Abstract # 1032.
Bork K, Hardt J. Hereditary angioedema: long-term treatment with one or more injections of C1 inhibitor concentrate per week. Int Arch Allergy Immunol. 2011;154:81–8.
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Bork, K. Current Management Options for Hereditary Angioedema. Curr Allergy Asthma Rep 12, 273–280 (2012). https://doi.org/10.1007/s11882-012-0273-4
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DOI: https://doi.org/10.1007/s11882-012-0273-4